Corona virus disease 2019(COVID-19)infection has become a major public health issue affecting human health.The main goal of epidemic prevention and control at the current stage in China is to“protect people’s health...Corona virus disease 2019(COVID-19)infection has become a major public health issue affecting human health.The main goal of epidemic prevention and control at the current stage in China is to“protect people’s health and prevent severe cases”.Patients with lung cancer who receive antitumor therapy have low immunity,and the risk of severe illness and death once infected is much higher than healthy people,so they are vulnerable to COVID-19 infection.At present,less attention has been paid to the prevention and treatment of COVID-19 infection in patients with lung cancer in domestic guidelines and consensus.Based on the published data in China and abroad,we proposed recommendations and formed expert consensus on the vaccination of COVID-19,the use of neutralizing antibodies and small molecule antiviral drugs for patients with lung cancer,for physician’s reference.展开更多
Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab ...Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for LA-NSCLC.Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging results.This review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable LA-NSCLC.Although the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i RT.These challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient cohorts.Furthermore,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.展开更多
Sulfamethoxazole(SMX)is an antibiotic and widely present in aquatic environments,so it presents a serious threat to human health and sustainable development.A dielectric barrier discharge(DBD)plasma jet was utilized t...Sulfamethoxazole(SMX)is an antibiotic and widely present in aquatic environments,so it presents a serious threat to human health and sustainable development.A dielectric barrier discharge(DBD)plasma jet was utilized to degrade aqueous SMX,and the effects of various operating parameters(working gas,discharge power,etc)on SMX degradation performance were studied.The experimental results showed that the DBD plasma jet can obtain a relatively high degradation efficiency for SMX when the discharge power is high with an oxygen atmosphere,the initial concentration of SMX is low,and the aqueous solution is under acidic conditions.The reactive species produced in the liquid phase were detected,and OH radicals and O3were found to play a significant role in the degradation of SMX.Moreover,the process of SMX degradation could be better fitted by the quasi-first-order reaction kinetic equation.The analysis of the SMX degradation process indicated that SMX was gradually decomposed and 4-amino benzene sulfonic acid,benzene sulfonamide,4-nitro SMX,and phenylsulfinyl acid were detected,and thus three possible degradation pathways were finally proposed.The mineralization degree of SMX reached 90.04%after plasma treatment for 20 min,and the toxicity of the solution fluctuated with the discharge time but eventually decreased.展开更多
Esophageal cancer usually has a poor prognosis.Given the significant breakthrough with tumor immunotherapy,an increasing number of clinical studies have demonstrated that the combination of radiotherapy and immune che...Esophageal cancer usually has a poor prognosis.Given the significant breakthrough with tumor immunotherapy,an increasing number of clinical studies have demonstrated that the combination of radiotherapy and immune checkpoint inhibitors(ICIs)may have a synergistic effect and good outcome in esophageal cancer.Clinical studies of immunoradiotherapy(iRT)for esophageal cancer have proliferated enormously from 2021 to the present.However,a summary of the efficacy and toxicity of combined therapy to guide esophageal cancer treatment in clinical practice is lacking.For this review,we integrate the latest data to analyze and assess the efficacy and safety of iRT for esophageal cancer.In addition,we discuss better predictive biomarkers,therapeutic options for specific populations,and other challenges to identify directions for future research design.展开更多
As immunotherapy has gained increasing interest as a new foundation for cancer therapy,some atypical response patterns,such as pseudoprogression and hyperprogression,have garnered the attention of physicians.Pseudopro...As immunotherapy has gained increasing interest as a new foundation for cancer therapy,some atypical response patterns,such as pseudoprogression and hyperprogression,have garnered the attention of physicians.Pseudoprogression is a phenomenon in which an initial increase in tumor size is observed or new lesions appear,followed by a decrease in tumor burden;this phenomenon can benefit patients receiving immunotherapy but often leads to premature discontinuation of treatment owing to the false judgment of progression.Accurately recognizing pseudoprogression is also a challenge for physicians.Because of the extensive attention on pseudoprogression,significant progress has been made.Some new criteria for immunotherapy,such as irRC,iRECIST and imRECIST,were proposed to accurately evaluate the response to immunotherapy.Many new detection indexes,such as ctDNA and IL-8,have also been used to identify pseudoprogression.In this review,the definition,evaluation criteria,mechanism,monitoring,management and prognosis of pseudoprogression are summarized,and diagnostic and treatment processes for patients with progression but with a suspicion of pseudoprogression are proposed;these processes could be helpful for physicians in clinical practice and enhances the understanding of pseudoprogression.展开更多
Objective: We investigated the correlation between the number of circulating tumor cells(CTCs) and wholebody metabolic tumor volume(WBMTV) measured by 18 F-fluorodeoxyglucose(FDG) positron emission tomography/computed...Objective: We investigated the correlation between the number of circulating tumor cells(CTCs) and wholebody metabolic tumor volume(WBMTV) measured by 18 F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT).The aim was to evaluate the value of the incorporation of CTC number and WBMTV in the prognostic prediction of stage III small-cell lung cancer(SCLC).Methods: One hundred and twenty-nine patients were enrolled in this study.All patients were treated with four cycles of a platinum-based regimen and concurrent chest irradiation,followed by prophylactic cranial irradiation.Blood samples for CTC analysis were obtained from 112 patients before the initiation of chemotherapy(as a baseline),after cycle 1 and after cycle 4.CTCs were measured using the CELLSEARCH? system.The patients underwent pretreatment FDG PET/CT WBMTV,which included all malignant lesions.The Spearman rank test was used to determine the correlation among CTC counts,WBMTV and disease stage.Overall survival(OS) and progression-free survival(PFS) curves were produced using the Kaplan-Meier method,and survival differences between groups were assessed by the log-rank test.Results: The number of CTCs at baseline did not correlate with WBMTV before the initiation of therapy(P=0.241).The number of CTCs at baseline and the WBMTV before the initiation of therapy were independent relevant factors for PFS and OS.The subgroup analysis(Group A: CTC count >19.5 and a WBMTV >266.5cm^3;Group B: CTC count >19.5 and a WBMTV ≤266.5cm^3; Group C: CTC count ≤19.5 and a WBMTV >266.5cm^3;Group D: CTC count ≤19.5 and a WBMTV ≤266.5cm^3) showed that the differences were statistically significant in the median PFS(Group A vs.D,P<0.001; Group B vs.D,P=0.018; Group C vs.D,P=0.029) and in the median OS(Group A vs.D,P<0.001; Group B vs.D,P=0.012).Conclusions: CTC number and WBMTV are related to progression and death in patients with SCLC.The incorporation of CTC number and WBMTV scans can provide a detailed prognostic prediction for SCLC.展开更多
Late embryogenesis abundant(LEA)proteins play an important role in plant growth and development,as well as in the plant response to various abiotic stresses.In this study,CsLEA1,a novel gene encoding a LEA_3 subfamily...Late embryogenesis abundant(LEA)proteins play an important role in plant growth and development,as well as in the plant response to various abiotic stresses.In this study,CsLEA1,a novel gene encoding a LEA_3 subfamily protein,was successfully cloned froma tea plant[Camellia sinensis(L.)O.Kuntze].Bioinformatics analysis and prokaryotic expression assays showed that CsLEA1 is a typical hydrophilic protein with a molecular weight of approximately 10.4 kD.Expression analyses revealed that the transcription of CsLEA1 in C.sinensis leaves was significantly induced by cold stress.In addition,the heterologous expression of CsLEA1 increased the tolerance of Escherichia coli and yeast to cold stress,which might be closely related to the low molecular weight and high hydrophilicity of the CsLEA1.Taken together,our results suggest that CsLEA1 might have an important function in the tolerance of C.sinensis to cold stress,thus providing a potential application in molecular breeding to enhance the cold stress tolerance of tea plants.展开更多
Objective:The aims of this study were to evaluate potential side effects of 18F-fluoroerythronitroimidazole (18F-FETNIM) as a new-type hypoxia-imaging agent and to investigate the feasibility of 18F-FETNIM PET imaging...Objective:The aims of this study were to evaluate potential side effects of 18F-fluoroerythronitroimidazole (18F-FETNIM) as a new-type hypoxia-imaging agent and to investigate the feasibility of 18F-FETNIM PET imaging in advanced non-small cell lung cancer (NSCLC) patients and the correlations of hypoxia extent with tumor volume or pathological type. Methods: Twenty-six NSCLC patients were prospectively included in the study. PET/CT scans were performed 2 h after intravenous injection of 18F-FETNIM in all 26 patients. A pixel-by-pixel calculation of tumor to blood (T/B) activity ratio for all image planes was calculated. The number of pixels in the tumor volume with a T/B ratio≥ 1.5,indicating significant hypoxia,was determined and converted to mL units to measure the hypoxia volume (HV). Results: The images were clearly identified after 2 h post-injection of 18F-FETNIM. The tumors in 4 cases were not distinguished from background,while the remaining 22 displayed local 18F-FETNIM uptake in thoracic lesions moderately to markedly higher than background. There was no correlation between 18F-FETNIM uptake with pathological type. There were significant correlations of HV and also the T/B ratio with tumor volume. Conclusion:18F-FETNIM is a promising hypoxia-imaging agent which clinical use is safe and satisfactory. The preliminary study provides valuable methods and experience to its further research.展开更多
Purpose: To evaluate the current status of stereotactic body radiotherapy (SBRT) for early staged non-small cell lung cancer (NSCLC) at main cancer hospitals in China. Methods and Materials: The questionnaire was sent...Purpose: To evaluate the current status of stereotactic body radiotherapy (SBRT) for early staged non-small cell lung cancer (NSCLC) at main cancer hospitals in China. Methods and Materials: The questionnaire was sent by mail and email to 21 hospitals, which include the patient enrollment, treatment technique, dose and fractionation, quality control, disease control and side effects. Results: Nineteen hospitals responded. It was found that SBRT has been used for early staged NSCLC in most of the hospitals participating in the survey. The patient characteristics and techniques were relatively consistent, but there were many controversies regarding dose fractionation and quality control. Conclusions: SBRT for early staged NSCLC has been applied at main cancer hospitals in China. However, considerable variation exists. The establishment of clinical guidelines and standardized quality control are crucial for further improvement.展开更多
Radiochemotherapy(RCT)is a powerful treatment for cervical cancer,which affects not only malignant cells but also the immune and stromal compartments of the tumor.Understanding the remodeling of the local ecosystem in...Radiochemotherapy(RCT)is a powerful treatment for cervical cancer,which affects not only malignant cells but also the immune and stromal compartments of the tumor.Understanding the remodeling of the local ecosystem induced by RCT would provide valuable insights into improving treatment strategies for cervical cancer.In this study,we applied single-cell RNA-sequencing to paired pre-and post-RCT tumor biopsies from patients with cervical cancer and adjacent normal cervical tissues.We found that the residual population of epithelial cells post-RCT showed upregulated expression of MHC class II genes.Moreover,RCT led to the accumulation of monocytic myeloid-derived suppressor cells with increased pro-inflammatory features and CD16+NK cells with a higher cytotoxic gene expression signature.However,subclusters of T cells showed no significant increase in the expression of cytotoxic features post-RCT.These results reveal the complex responses of the tumor ecosystem to RCT,providing evidence of activation of innate immunity and MHC-II upregulation in cervical cancer.展开更多
The efficacy of immunotherapy for advanced non-small cell lung cancer(NSCLC)remains unsatisfactory,as the majority of patients either do not experience an objective response or acquire secondary resistance.As a result...The efficacy of immunotherapy for advanced non-small cell lung cancer(NSCLC)remains unsatisfactory,as the majority of patients either do not experience an objective response or acquire secondary resistance.As a result,several methods to enhance the systemic efficacy of immunotherapy have been investigated,including a large area of active research by combining immunotherapy with radiation therapy(RT).Given the rapidly burgeoning concept of combining immunotherapy and RT for increasing therapeutic benefit,we review the progress in this field thus far and explore further avenues for enhancing this combination.This review commences with a discussion of the only two existing randomized trials(and a pooled analysis)showing that the addition of RT to immunotherapy improves the abscopal response rate,progression-free survival,and overall survival in metastatic NSCLC patients.We then discussed factors and biomarkers that may be associated with a proportionally greater benefit to additional RT,such as low programmed cell death protein ligand 1(PD-L1)status,tumor mutational burden(TMB),and patient’s immune function.Next,the implementation of RT to overcome immunotherapy resistance is discussed,including a mechanistic discussion and methods with which these mechanisms could be exploited.Lastly,the emerging role of low-dose RT is discussed,which may help to overcome inhibitory signals in the tumor stroma that limit T-cell infiltration.Taken together,given the current state of this rapidly expanding realm,these futuristic strategies may be reflected upon to further enhance the efficacy of immunotherapy for a wider group of patients.展开更多
Background:Second-generation programmed cell death-protein 1/pro-grammed death-ligand 1(PD-1/PD-L1)inhibitors,such as bintrafusp alfa(M7824),SHR-1701,and YM101,have been developed to simultaneously block PD-1/PD-L1 an...Background:Second-generation programmed cell death-protein 1/pro-grammed death-ligand 1(PD-1/PD-L1)inhibitors,such as bintrafusp alfa(M7824),SHR-1701,and YM101,have been developed to simultaneously block PD-1/PD-L1 and transforming growth factor-beta/transforming growth factor-beta receptor(TGF-P/TGF-βR).Consequently,it is necessary to identify predictive factors of lung cancer patients who are not only resistant to PD-1/PD-LI inhibitors but also sensitive to bifunctional drugs.The purpose of this study was to search for such predictors.Methods:Multivariable Cox regression was used to study the association between the clinical outcome of treatment with PD-1/PD-L1 inhibitors and lym-phocyte recovery after lymphopenia in lung cancer patients.Murine CMT167 lung cancer cells were engineered to express the firefly luciferase gene and implanted orthotopically in the lung of syngeneic mice.Bioluminescence imag-ing,flow cytometry,and immunohistochemistry were employed to detrmine response to immunotherapy and function of tumor-infiltrating immune cells.Results:For lung cancer patients treated with anti-PD-1/PD-LI antibodies,poor lymphocyte recovery was associated with a shorter progression-free survival(PFS;P<0.001),an accumulation of regulatory T cells(Tregs),and an elimi-nation of CD8+T cells in the peripheral blood.Levels of CD8+T cells and Treg cells were also imbalanced in the tumors and peripheral immune organs of mice with poor lymphocyte recovery after chemotherapy.Moreover,these mice failed to respond to anti-PD-1 antibodies but remained sensitive to the anti-PD-LI/TGF-βR fusion protein(SHR-1701).Consistently,SHR-1701 but not anti-PD-1 antibod-ies,markedly enhanced IFN-γproduction and Ki-67 expression in peripheral CD8+T cells from patients with impaired lymphocyte recovery.Conclusions:Lung cancer patients with poor lymphocyte recovery and suffer-ing from persistent lymphopenia after previous chemotherapy are resistant to anti-PD-1/PD-L1 antibodies but might be sensitive to second-generation agents such as SHR-1701.展开更多
Over the past few years,immune checkpoint inhibitors(ICIs)have greatly improved the survival for patients with non-small cell lung cancer(NSCLC)without driver mutations.Compared with wild-type tumors,tumors with epide...Over the past few years,immune checkpoint inhibitors(ICIs)have greatly improved the survival for patients with non-small cell lung cancer(NSCLC)without driver mutations.Compared with wild-type tumors,tumors with epidermal growth factor receptor(EGFR)mutations show more heterogeneity in the expression level of programmed cell death-ligand 1(PD-L1),tumor mutational burden(TMB),and other immune microenvironment characteristics.Whether ICIs are suitable for NSCLC patients with EGFR mutations is still worth exploring.In previous studies,no significantly improved benefits were observed with immunotherapy monotherapy in NSCLC patients with EGFR mutation.Here,we summarized and analyzed data from the clinical trials of ICIs or combined therapy in NSCLC patients with EGFR mutations.We also focused on the mechanisms affecting the efficacy of ICIs in NSCLC patients with EGFR mutations,the characteristics of potential responders,and provided insights into areas worth further investigations in future studies.展开更多
Radiotherapy(RT)is delivered for purposes of local control,but can also exert systemic effect on remote and non-irradiated tumor deposits,which is called abscopal effect.The view of RT as a simple local treatment has ...Radiotherapy(RT)is delivered for purposes of local control,but can also exert systemic effect on remote and non-irradiated tumor deposits,which is called abscopal effect.The view of RT as a simple local treatment has dramatically changed in recent years,and it is now widely accepted that RT can provoke a systemic immune response which gives a strong rationale for the combination of RT and immunotherapy(iRT).Nevertheless,several points remain to be addressed such as the interaction of RT and immune system,the identification of the best schedules for combination with immunotherapy(IO),the expansion of abscopal effect and the mechanism to amplify iRT.To answer these crucial questions,we roundly summarize underlying rationale showing the whole immune landscape in RT and clinical trials to attempt to identify the best schedules of iRT.In consideration of the rarity of abscopal effect,we propose that the occurrence of abscopal effect induced by radiation can be promoted to 100%in view of molecular and genetic level.Furthermore,the“radscopal effect”which refers to using low-dose radiation to reprogram the tumor microenvironment may amplify the occurrence of abscopal effect and overcome the resistance of iRT.Taken together,RT could be regarded as a trigger of systemic antitumor immune response,and with the help of IO can be used as a radical and systemic treatment and be added into current standard regimen of patients with metastatic cancer.展开更多
Bevacizumab,an anti-VEGF monoclonal antibody,has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC(ns-NSCLC).However,the safety and efficacy of bevacizumab for elderly patients ...Bevacizumab,an anti-VEGF monoclonal antibody,has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC(ns-NSCLC).However,the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation.Thus,59 patients were included in the present retrospective study,22 patients in the bevacizumab plus pemetrexed and platinum(B+PP)group,and 37 patients in the pemetrexed and platinum(PP)group.For the entire cohort of patients,the median OS was 33.3 months,and the 1-year and 2-year overall survival rates were 88.5%and 67.8%,respectively.The median OS and 1-year and 2-year OS rates were 20.5 months,70.3%and 0%,respectively,in the B+PP group and 33.4 months,97.0%and 89.4%,respectively,in the PP group(P<0.001).The incidence of grade≥3 adverse events was higher in the B+PP group than in the PP group(27.3%vs.10.8%,respectively;P=0.204).Univariate and multivariate analyses suggested that the receipt of≥5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS,whereas the addition of bevacizumab was an unfavorable prognostic factor.With increased toxicities,the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.展开更多
Background:Currently,due to synergy enhancement of anti-tumor effects and potent stimulation of abscopal effects,combination therapy with irradiation and programmed cell death protein 1/programmed death-ligand 1(PD-1/...Background:Currently,due to synergy enhancement of anti-tumor effects and potent stimulation of abscopal effects,combination therapy with irradiation and programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1)immune checkpoint inhibition(immuno-radiotherapy,iRT)has revolutionized the therapeutic guidelines.It has been demonstrated that tumor-draining lymph nodes(TDLN)are essential for effective antitumor immunity induced by radiotherapy,immunotherapy,or iRT.Given that the function of TDLN in iRT remains unclear,this study aimed to investigate the function and mechanism of TDLN in iRT-induced abscopal effects.Methods:The function of TDLN was evaluated using unilateral or bilateral MC38 and B16F10 subcutaneous tumor models with or without indicated TDLN.The flow cytometry,multiple immunofluorescence analysis,and NanoString analysis were utilized to detect the composition and function of the immune cells in the primary and abscopal tumor microenvironment.Additionally,we tempted to interrogate the possible mechanisms via RNA-sequencing of tumor-infiltrating lymphocytes and TDLN.Results:TDLN deficiency impaired the control of tumor growth by monotherapy.Bilateral TDLN removal rather than unilateral TDLN removal substantially curtailed iRT-stimulated anti-tumor and abscopal effects.Furthermore,in the absence of TDLN,the infiltration of CD45+and CD8+T cells was substantially reduced in both primary and abscopal tumors,and the anti-tumor function of CD8+T cells was attenuated as well.Additionally,the polarization of tumor-associated macrophages in primary and abscopal tumors were found to be dependent on intact bilateral TDLN.RNA-sequencing data indicated that impaired infiltration and anti-tumor effects of immune cells partially attributed to the altered secretion of components from the tumor microenvironment.Conclusions:TDLN play a critical role in iRT by promoting the infiltration of CD8+T cells and maintaining the M1/M2 macrophage ratio.展开更多
Trimodality based on neoadjuvant chemoradiotherapy(nCRT)followed by surgery is gaining popularity as a treatment strategy for locally advanced esophageal cancer.In this review,we summarize the role of nCRT and the rec...Trimodality based on neoadjuvant chemoradiotherapy(nCRT)followed by surgery is gaining popularity as a treatment strategy for locally advanced esophageal cancer.In this review,we summarize the role of nCRT and the recommended nCRT regimens based on clinical trials and meta-analyses.We analyze the relationship of nCRT with pathologic complete response(pCR)and then identify potential predictive markers of response.Compared with surgery alone and neoadjuvant chemotherapy followed by surgery,trimodality provides longer survival and has the advantage of local control compared with definitive chemoradiotherapy.The standard regimen is a platinum-based regimen with a radiation dose range of 41.4–50.4 Gy by conventional fractionation.Evidence shows that patients with pCR tend to live longer than non-responders,indicating that pCR is a significant prognostic factor for patients with esophageal cancer.Individualized medicine requires predictive markers of individual patients based on their own genes.Currently,no definite marker is proved to be sufficiently sensitive and specific for use in clinical practice,although 18-fluorodeoxyglucose positron emission tomography shows promise in predicting response to nCRT.展开更多
Epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective targeted therapy drugs for advanced nonsmall cell lung cancer(NSCLC)patients carrying sensitized EGFR mutations.The rapid developmen...Epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective targeted therapy drugs for advanced nonsmall cell lung cancer(NSCLC)patients carrying sensitized EGFR mutations.The rapid development of EGFR-TKIs resistance represents a major clinical challenge for managing NSCLC.The chromosome 4q12 is the first genome-wide association study(GWAS)-reported locus associated with progression-free survival(PFS)of NSCLC patients treated with EGFR-TKIs.However,the biological significance of the noncoding transcripts at 4q12 in NSCLC remains elusive.In the present study,we identified two 4q12 long noncoding RNAs(lncRNAs)LCETRL3 and LCETRL4 which could significantly dimmish EGFR-TKIs efficiency.In line with their oncogenic role,evidently higher LCETRL3 and LCETRL4 levels were observed in NSCLC tissues as compared with normal specimens.Importantly,lncRNA LCETRL3 can interact with oncoprotein TDP43 and inhibit ubiquitination and degradation of TDP43.Similarly,lncRNA LCETRL4 can bind and stabilize oncoprotein EIF2S1 through reducing ubiquitin-proteasome degradation of EIF2S1.In particular,elevated levels of LCETRL3 or LCETRL4 in NSCLC cells resulted in stabilization of TDP43 or EIF2S1,increased levels of NOTCH1 or phosphorylated PDK1,activated AKT signaling and,thus,EGFR-TKIs resistance.Taken together,our data revealed a novel model that integrates two lncRNAs transcribed from the 4q12 locus into the regulation of EGFR-TKIs resistance in NSCLC.These findings shed new light on the importance of functionally annotating lncRNAs in the GWAS loci and provided insights to declare novel druggable targets,i.e.,lncRNAs,which may unlock the therapeutic potential of EGFR-TKIs resistant NSCLC in the clinic.展开更多
Dear Editor,Increasing numbers of studies have revealed the immunomodulating effects of radiotherapy when combined with immune checkpoint inhibitors,as radioimmunotherapy has proven to be a promising treatment[1].Radi...Dear Editor,Increasing numbers of studies have revealed the immunomodulating effects of radiotherapy when combined with immune checkpoint inhibitors,as radioimmunotherapy has proven to be a promising treatment[1].Radioimmunotherapy has shown significantly improved tumor responses than radiotherapy or immunotherapy alone in various malignant tumors[2–4].It has also been applied to cervical cancer in multiple ongoing clinical trials(NCT03612791[5]and NCT02635360[6]).However,tumor recurrence andmetastasis are often unavoidable.As such,investigations into radioimmunotherapy-induced tumor ecosystem evolution are essential for guiding improvements in treatment strategies that achieve better long-term disease control.To date,several studies have investigated radiochemotherapy-induced tumor ecosystem evolution using bulk RNA-sequencing and immune staining[7,8].However,these findings were limited owing to the cellular heterogeneity in cancers.Single-cell RNA-sequencing(scRNA-seq)enables the characterization of cell compositions and transcriptomic states in the tumor at single-cell resolution.展开更多
文摘Corona virus disease 2019(COVID-19)infection has become a major public health issue affecting human health.The main goal of epidemic prevention and control at the current stage in China is to“protect people’s health and prevent severe cases”.Patients with lung cancer who receive antitumor therapy have low immunity,and the risk of severe illness and death once infected is much higher than healthy people,so they are vulnerable to COVID-19 infection.At present,less attention has been paid to the prevention and treatment of COVID-19 infection in patients with lung cancer in domestic guidelines and consensus.Based on the published data in China and abroad,we proposed recommendations and formed expert consensus on the vaccination of COVID-19,the use of neutralizing antibodies and small molecule antiviral drugs for patients with lung cancer,for physician’s reference.
基金funded by the National Natural Science Foundation of China(Grant Nos.81972796,82272845,81972863,and 82030082)the Key Research and Development Program of Shandong(Major Science&Technology Innovation Project Grant No.2021SFGC0501)+1 种基金the CSCO-Haosen Foundation(Grant No.Y-HS202102-0089)the CSCO-Xinda Foundation(Grant No.Y-XD202001-0008)。
文摘Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for LA-NSCLC.Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging results.This review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable LA-NSCLC.Although the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i RT.These challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient cohorts.Furthermore,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.
基金supported jointly by National Natural Science Foundation of China(Nos.U20A20372,51807046,51777206)the Natural Science Foundation of Anhui Province(Nos.2108085MD136,1908085MA29)。
文摘Sulfamethoxazole(SMX)is an antibiotic and widely present in aquatic environments,so it presents a serious threat to human health and sustainable development.A dielectric barrier discharge(DBD)plasma jet was utilized to degrade aqueous SMX,and the effects of various operating parameters(working gas,discharge power,etc)on SMX degradation performance were studied.The experimental results showed that the DBD plasma jet can obtain a relatively high degradation efficiency for SMX when the discharge power is high with an oxygen atmosphere,the initial concentration of SMX is low,and the aqueous solution is under acidic conditions.The reactive species produced in the liquid phase were detected,and OH radicals and O3were found to play a significant role in the degradation of SMX.Moreover,the process of SMX degradation could be better fitted by the quasi-first-order reaction kinetic equation.The analysis of the SMX degradation process indicated that SMX was gradually decomposed and 4-amino benzene sulfonic acid,benzene sulfonamide,4-nitro SMX,and phenylsulfinyl acid were detected,and thus three possible degradation pathways were finally proposed.The mineralization degree of SMX reached 90.04%after plasma treatment for 20 min,and the toxicity of the solution fluctuated with the discharge time but eventually decreased.
基金supported by National Natural Science Foundation of China(No.82172865)Clinical Research Special Fund of Wu Jieping Medical Foundation(No.320.6750.2021-02-51 and 320.6750.2021-17-13).
文摘Esophageal cancer usually has a poor prognosis.Given the significant breakthrough with tumor immunotherapy,an increasing number of clinical studies have demonstrated that the combination of radiotherapy and immune checkpoint inhibitors(ICIs)may have a synergistic effect and good outcome in esophageal cancer.Clinical studies of immunoradiotherapy(iRT)for esophageal cancer have proliferated enormously from 2021 to the present.However,a summary of the efficacy and toxicity of combined therapy to guide esophageal cancer treatment in clinical practice is lacking.For this review,we integrate the latest data to analyze and assess the efficacy and safety of iRT for esophageal cancer.In addition,we discuss better predictive biomarkers,therapeutic options for specific populations,and other challenges to identify directions for future research design.
基金support by the National Key Research and Development Program of China (Grant No. 2018YFC1313201)
文摘As immunotherapy has gained increasing interest as a new foundation for cancer therapy,some atypical response patterns,such as pseudoprogression and hyperprogression,have garnered the attention of physicians.Pseudoprogression is a phenomenon in which an initial increase in tumor size is observed or new lesions appear,followed by a decrease in tumor burden;this phenomenon can benefit patients receiving immunotherapy but often leads to premature discontinuation of treatment owing to the false judgment of progression.Accurately recognizing pseudoprogression is also a challenge for physicians.Because of the extensive attention on pseudoprogression,significant progress has been made.Some new criteria for immunotherapy,such as irRC,iRECIST and imRECIST,were proposed to accurately evaluate the response to immunotherapy.Many new detection indexes,such as ctDNA and IL-8,have also been used to identify pseudoprogression.In this review,the definition,evaluation criteria,mechanism,monitoring,management and prognosis of pseudoprogression are summarized,and diagnostic and treatment processes for patients with progression but with a suspicion of pseudoprogression are proposed;these processes could be helpful for physicians in clinical practice and enhances the understanding of pseudoprogression.
基金supported by a grant from the National Health and Family Planning Commission of China(No.201402011)
文摘Objective: We investigated the correlation between the number of circulating tumor cells(CTCs) and wholebody metabolic tumor volume(WBMTV) measured by 18 F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT).The aim was to evaluate the value of the incorporation of CTC number and WBMTV in the prognostic prediction of stage III small-cell lung cancer(SCLC).Methods: One hundred and twenty-nine patients were enrolled in this study.All patients were treated with four cycles of a platinum-based regimen and concurrent chest irradiation,followed by prophylactic cranial irradiation.Blood samples for CTC analysis were obtained from 112 patients before the initiation of chemotherapy(as a baseline),after cycle 1 and after cycle 4.CTCs were measured using the CELLSEARCH? system.The patients underwent pretreatment FDG PET/CT WBMTV,which included all malignant lesions.The Spearman rank test was used to determine the correlation among CTC counts,WBMTV and disease stage.Overall survival(OS) and progression-free survival(PFS) curves were produced using the Kaplan-Meier method,and survival differences between groups were assessed by the log-rank test.Results: The number of CTCs at baseline did not correlate with WBMTV before the initiation of therapy(P=0.241).The number of CTCs at baseline and the WBMTV before the initiation of therapy were independent relevant factors for PFS and OS.The subgroup analysis(Group A: CTC count >19.5 and a WBMTV >266.5cm^3;Group B: CTC count >19.5 and a WBMTV ≤266.5cm^3; Group C: CTC count ≤19.5 and a WBMTV >266.5cm^3;Group D: CTC count ≤19.5 and a WBMTV ≤266.5cm^3) showed that the differences were statistically significant in the median PFS(Group A vs.D,P<0.001; Group B vs.D,P=0.018; Group C vs.D,P=0.029) and in the median OS(Group A vs.D,P<0.001; Group B vs.D,P=0.012).Conclusions: CTC number and WBMTV are related to progression and death in patients with SCLC.The incorporation of CTC number and WBMTV scans can provide a detailed prognostic prediction for SCLC.
基金This work was supported by the China Postdoctoral Science Foundation(Grant No.2016M602873)the Fundamental Research Funds for the Central Universities(Grant No.2452016182,2452017074)+1 种基金the earmarked fund for Modern Agro-industry Technology Research System(Grant No.CARS-19)the special fund for University-Supported Extension Model(Grant No.TGZX2018-39).
文摘Late embryogenesis abundant(LEA)proteins play an important role in plant growth and development,as well as in the plant response to various abiotic stresses.In this study,CsLEA1,a novel gene encoding a LEA_3 subfamily protein,was successfully cloned froma tea plant[Camellia sinensis(L.)O.Kuntze].Bioinformatics analysis and prokaryotic expression assays showed that CsLEA1 is a typical hydrophilic protein with a molecular weight of approximately 10.4 kD.Expression analyses revealed that the transcription of CsLEA1 in C.sinensis leaves was significantly induced by cold stress.In addition,the heterologous expression of CsLEA1 increased the tolerance of Escherichia coli and yeast to cold stress,which might be closely related to the low molecular weight and high hydrophilicity of the CsLEA1.Taken together,our results suggest that CsLEA1 might have an important function in the tolerance of C.sinensis to cold stress,thus providing a potential application in molecular breeding to enhance the cold stress tolerance of tea plants.
文摘Objective:The aims of this study were to evaluate potential side effects of 18F-fluoroerythronitroimidazole (18F-FETNIM) as a new-type hypoxia-imaging agent and to investigate the feasibility of 18F-FETNIM PET imaging in advanced non-small cell lung cancer (NSCLC) patients and the correlations of hypoxia extent with tumor volume or pathological type. Methods: Twenty-six NSCLC patients were prospectively included in the study. PET/CT scans were performed 2 h after intravenous injection of 18F-FETNIM in all 26 patients. A pixel-by-pixel calculation of tumor to blood (T/B) activity ratio for all image planes was calculated. The number of pixels in the tumor volume with a T/B ratio≥ 1.5,indicating significant hypoxia,was determined and converted to mL units to measure the hypoxia volume (HV). Results: The images were clearly identified after 2 h post-injection of 18F-FETNIM. The tumors in 4 cases were not distinguished from background,while the remaining 22 displayed local 18F-FETNIM uptake in thoracic lesions moderately to markedly higher than background. There was no correlation between 18F-FETNIM uptake with pathological type. There were significant correlations of HV and also the T/B ratio with tumor volume. Conclusion:18F-FETNIM is a promising hypoxia-imaging agent which clinical use is safe and satisfactory. The preliminary study provides valuable methods and experience to its further research.
文摘Purpose: To evaluate the current status of stereotactic body radiotherapy (SBRT) for early staged non-small cell lung cancer (NSCLC) at main cancer hospitals in China. Methods and Materials: The questionnaire was sent by mail and email to 21 hospitals, which include the patient enrollment, treatment technique, dose and fractionation, quality control, disease control and side effects. Results: Nineteen hospitals responded. It was found that SBRT has been used for early staged NSCLC in most of the hospitals participating in the survey. The patient characteristics and techniques were relatively consistent, but there were many controversies regarding dose fractionation and quality control. Conclusions: SBRT for early staged NSCLC has been applied at main cancer hospitals in China. However, considerable variation exists. The establishment of clinical guidelines and standardized quality control are crucial for further improvement.
基金This study was supported by funds from the National Natural Science Foundation of China(82030082 and 81871895)the Academic Promotion Program of Shandong First Medical University(2019ZL002)+4 种基金Key Research and Development Project of Shandong Province of China(2021CXGC011102)the Radiation Oncology Innovate Unit,Chinese Academy of Medical Sciences(2019RU071)Young Taishan Scholars and Academic Promotion Program of Shandong First Medical University(2019RC003)Shandong Provincial Natural Science Foundation(ZR2021QH006)Beijing Bethune Charitable Foundation(flzh202118).
文摘Radiochemotherapy(RCT)is a powerful treatment for cervical cancer,which affects not only malignant cells but also the immune and stromal compartments of the tumor.Understanding the remodeling of the local ecosystem induced by RCT would provide valuable insights into improving treatment strategies for cervical cancer.In this study,we applied single-cell RNA-sequencing to paired pre-and post-RCT tumor biopsies from patients with cervical cancer and adjacent normal cervical tissues.We found that the residual population of epithelial cells post-RCT showed upregulated expression of MHC class II genes.Moreover,RCT led to the accumulation of monocytic myeloid-derived suppressor cells with increased pro-inflammatory features and CD16+NK cells with a higher cytotoxic gene expression signature.However,subclusters of T cells showed no significant increase in the expression of cytotoxic features post-RCT.These results reveal the complex responses of the tumor ecosystem to RCT,providing evidence of activation of innate immunity and MHC-II upregulation in cervical cancer.
基金The study was supported by funds from The National Key Research and Development Projects of China(2018YFC1312201)Radiation Oncology Innovate Unit,Chinese Academy of Medical Sciences(2019RU071)+2 种基金Academic Promotion Program of Shandong First Medical University(2019ZL002)Foundation of National Natural Science Foundation of China(81972863,81627901 and 82030082)Science Foundation of Shandong(ZR2020 LZL016).
文摘The efficacy of immunotherapy for advanced non-small cell lung cancer(NSCLC)remains unsatisfactory,as the majority of patients either do not experience an objective response or acquire secondary resistance.As a result,several methods to enhance the systemic efficacy of immunotherapy have been investigated,including a large area of active research by combining immunotherapy with radiation therapy(RT).Given the rapidly burgeoning concept of combining immunotherapy and RT for increasing therapeutic benefit,we review the progress in this field thus far and explore further avenues for enhancing this combination.This review commences with a discussion of the only two existing randomized trials(and a pooled analysis)showing that the addition of RT to immunotherapy improves the abscopal response rate,progression-free survival,and overall survival in metastatic NSCLC patients.We then discussed factors and biomarkers that may be associated with a proportionally greater benefit to additional RT,such as low programmed cell death protein ligand 1(PD-L1)status,tumor mutational burden(TMB),and patient’s immune function.Next,the implementation of RT to overcome immunotherapy resistance is discussed,including a mechanistic discussion and methods with which these mechanisms could be exploited.Lastly,the emerging role of low-dose RT is discussed,which may help to overcome inhibitory signals in the tumor stroma that limit T-cell infiltration.Taken together,given the current state of this rapidly expanding realm,these futuristic strategies may be reflected upon to further enhance the efficacy of immunotherapy for a wider group of patients.
基金NationalKeyResearch and Develop-ment Projects of China,Grant/Award Number:2018YFC1312201Academic Promotion Programof Shandong First Medical University,Grant/AwardNum-ber:2019ZL002+3 种基金NationalNatural Sci-ence Foundation of China,Grant/Award Numbers:81803096,81972863,81627901,82030082Natural Science Foundation of Shandong Province,Grant/AwardNum-ber:ZR201807080057Cancer Institute and Hospital,ChineseAcademy of Medical Sci-ences,Grant/Award Number:2019RU071supported by funding from the Shandong Provincial Natural Science Foundation(ZR201807080057),the National Key Research and Development Projects of China(2018YFC1312201),Cancer Institute and Hospital,Chinese Academy of Medical Sciences(2019RU071),the Academic Promotion Program of Shandong First Medical University(2019ZL002),and the National Natural Science Foundation of China(81803096,81972863,81627901,and 82030082).
文摘Background:Second-generation programmed cell death-protein 1/pro-grammed death-ligand 1(PD-1/PD-L1)inhibitors,such as bintrafusp alfa(M7824),SHR-1701,and YM101,have been developed to simultaneously block PD-1/PD-L1 and transforming growth factor-beta/transforming growth factor-beta receptor(TGF-P/TGF-βR).Consequently,it is necessary to identify predictive factors of lung cancer patients who are not only resistant to PD-1/PD-LI inhibitors but also sensitive to bifunctional drugs.The purpose of this study was to search for such predictors.Methods:Multivariable Cox regression was used to study the association between the clinical outcome of treatment with PD-1/PD-L1 inhibitors and lym-phocyte recovery after lymphopenia in lung cancer patients.Murine CMT167 lung cancer cells were engineered to express the firefly luciferase gene and implanted orthotopically in the lung of syngeneic mice.Bioluminescence imag-ing,flow cytometry,and immunohistochemistry were employed to detrmine response to immunotherapy and function of tumor-infiltrating immune cells.Results:For lung cancer patients treated with anti-PD-1/PD-LI antibodies,poor lymphocyte recovery was associated with a shorter progression-free survival(PFS;P<0.001),an accumulation of regulatory T cells(Tregs),and an elimi-nation of CD8+T cells in the peripheral blood.Levels of CD8+T cells and Treg cells were also imbalanced in the tumors and peripheral immune organs of mice with poor lymphocyte recovery after chemotherapy.Moreover,these mice failed to respond to anti-PD-1 antibodies but remained sensitive to the anti-PD-LI/TGF-βR fusion protein(SHR-1701).Consistently,SHR-1701 but not anti-PD-1 antibod-ies,markedly enhanced IFN-γproduction and Ki-67 expression in peripheral CD8+T cells from patients with impaired lymphocyte recovery.Conclusions:Lung cancer patients with poor lymphocyte recovery and suffer-ing from persistent lymphopenia after previous chemotherapy are resistant to anti-PD-1/PD-L1 antibodies but might be sensitive to second-generation agents such as SHR-1701.
基金The study was funded by the National Natural Science Foundation of China(81972796 and 81972863)Radiation Oncology Innovate Unit,Chinese Academy of Medical Sciences(2019RU071)+1 种基金the Academic Promotion Program of Shandong First Medical University(2019ZL002)the Natural Science Foundation of Shandong(ZR2019MH010 and ZR2020MH289).
文摘Over the past few years,immune checkpoint inhibitors(ICIs)have greatly improved the survival for patients with non-small cell lung cancer(NSCLC)without driver mutations.Compared with wild-type tumors,tumors with epidermal growth factor receptor(EGFR)mutations show more heterogeneity in the expression level of programmed cell death-ligand 1(PD-L1),tumor mutational burden(TMB),and other immune microenvironment characteristics.Whether ICIs are suitable for NSCLC patients with EGFR mutations is still worth exploring.In previous studies,no significantly improved benefits were observed with immunotherapy monotherapy in NSCLC patients with EGFR mutation.Here,we summarized and analyzed data from the clinical trials of ICIs or combined therapy in NSCLC patients with EGFR mutations.We also focused on the mechanisms affecting the efficacy of ICIs in NSCLC patients with EGFR mutations,the characteristics of potential responders,and provided insights into areas worth further investigations in future studies.
基金Dawei Chen has received grants from National Natural Science Foundation of China(82172676)the Young Elite Scientist Sponsorship Program by CAST(YESS20210137)+2 种基金Science Foundation of Shandong(ZR2021YQ52,ZR2020LZL016)Foundation of Bethune Charitable Foundation(2021434953)Jinming Yu has received grants from the foundation of National Natural Science Foundation of China(81627901,81972863,and 82030082)。
文摘Radiotherapy(RT)is delivered for purposes of local control,but can also exert systemic effect on remote and non-irradiated tumor deposits,which is called abscopal effect.The view of RT as a simple local treatment has dramatically changed in recent years,and it is now widely accepted that RT can provoke a systemic immune response which gives a strong rationale for the combination of RT and immunotherapy(iRT).Nevertheless,several points remain to be addressed such as the interaction of RT and immune system,the identification of the best schedules for combination with immunotherapy(IO),the expansion of abscopal effect and the mechanism to amplify iRT.To answer these crucial questions,we roundly summarize underlying rationale showing the whole immune landscape in RT and clinical trials to attempt to identify the best schedules of iRT.In consideration of the rarity of abscopal effect,we propose that the occurrence of abscopal effect induced by radiation can be promoted to 100%in view of molecular and genetic level.Furthermore,the“radscopal effect”which refers to using low-dose radiation to reprogram the tumor microenvironment may amplify the occurrence of abscopal effect and overcome the resistance of iRT.Taken together,RT could be regarded as a trigger of systemic antitumor immune response,and with the help of IO can be used as a radical and systemic treatment and be added into current standard regimen of patients with metastatic cancer.
基金supported by the National Key R&D Program of China(No.2018YFC1313201)the Innovation Project of Shandong Academy of Medical Sciences(No.2019-04)the Academic Promotion Program of Shandong First Medical University(No.2019ZL002).
文摘Bevacizumab,an anti-VEGF monoclonal antibody,has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC(ns-NSCLC).However,the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation.Thus,59 patients were included in the present retrospective study,22 patients in the bevacizumab plus pemetrexed and platinum(B+PP)group,and 37 patients in the pemetrexed and platinum(PP)group.For the entire cohort of patients,the median OS was 33.3 months,and the 1-year and 2-year overall survival rates were 88.5%and 67.8%,respectively.The median OS and 1-year and 2-year OS rates were 20.5 months,70.3%and 0%,respectively,in the B+PP group and 33.4 months,97.0%and 89.4%,respectively,in the PP group(P<0.001).The incidence of grade≥3 adverse events was higher in the B+PP group than in the PP group(27.3%vs.10.8%,respectively;P=0.204).Univariate and multivariate analyses suggested that the receipt of≥5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS,whereas the addition of bevacizumab was an unfavorable prognostic factor.With increased toxicities,the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.
基金the Academic Promotion Program of Shandong First Medical Univer-sity(2019ZL002)Research Unit of Radiation Oncology,Chinese Academy of Medical Sciences(2019RU071)+2 种基金the foundation of National Natural Science Foundation of China(81627901,81972863,82030082 and 31900649)the foundation of Natural Science Foundation of Shandong(ZR201911040452 and ZR2019LZL018)the Cancer Pre-vention and Treatment Joint Fund of Natural Science Foundation of Shandong Province(ZR2020LZL014).
文摘Background:Currently,due to synergy enhancement of anti-tumor effects and potent stimulation of abscopal effects,combination therapy with irradiation and programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1)immune checkpoint inhibition(immuno-radiotherapy,iRT)has revolutionized the therapeutic guidelines.It has been demonstrated that tumor-draining lymph nodes(TDLN)are essential for effective antitumor immunity induced by radiotherapy,immunotherapy,or iRT.Given that the function of TDLN in iRT remains unclear,this study aimed to investigate the function and mechanism of TDLN in iRT-induced abscopal effects.Methods:The function of TDLN was evaluated using unilateral or bilateral MC38 and B16F10 subcutaneous tumor models with or without indicated TDLN.The flow cytometry,multiple immunofluorescence analysis,and NanoString analysis were utilized to detect the composition and function of the immune cells in the primary and abscopal tumor microenvironment.Additionally,we tempted to interrogate the possible mechanisms via RNA-sequencing of tumor-infiltrating lymphocytes and TDLN.Results:TDLN deficiency impaired the control of tumor growth by monotherapy.Bilateral TDLN removal rather than unilateral TDLN removal substantially curtailed iRT-stimulated anti-tumor and abscopal effects.Furthermore,in the absence of TDLN,the infiltration of CD45+and CD8+T cells was substantially reduced in both primary and abscopal tumors,and the anti-tumor function of CD8+T cells was attenuated as well.Additionally,the polarization of tumor-associated macrophages in primary and abscopal tumors were found to be dependent on intact bilateral TDLN.RNA-sequencing data indicated that impaired infiltration and anti-tumor effects of immune cells partially attributed to the altered secretion of components from the tumor microenvironment.Conclusions:TDLN play a critical role in iRT by promoting the infiltration of CD8+T cells and maintaining the M1/M2 macrophage ratio.
基金supported by National Natural Science Foundation of China(Grant No.81101700).
文摘Trimodality based on neoadjuvant chemoradiotherapy(nCRT)followed by surgery is gaining popularity as a treatment strategy for locally advanced esophageal cancer.In this review,we summarize the role of nCRT and the recommended nCRT regimens based on clinical trials and meta-analyses.We analyze the relationship of nCRT with pathologic complete response(pCR)and then identify potential predictive markers of response.Compared with surgery alone and neoadjuvant chemotherapy followed by surgery,trimodality provides longer survival and has the advantage of local control compared with definitive chemoradiotherapy.The standard regimen is a platinum-based regimen with a radiation dose range of 41.4–50.4 Gy by conventional fractionation.Evidence shows that patients with pCR tend to live longer than non-responders,indicating that pCR is a significant prognostic factor for patients with esophageal cancer.Individualized medicine requires predictive markers of individual patients based on their own genes.Currently,no definite marker is proved to be sufficiently sensitive and specific for use in clinical practice,although 18-fluorodeoxyglucose positron emission tomography shows promise in predicting response to nCRT.
基金This work was supported by Taishan Scholars Program of Shandong Province(tsqn20161060)(to M.Y.)National Natural Science Foundation of China(82173070 and 31871306)(to M.Y.)+1 种基金Natural Science Foundation of Shandong Province(ZR2021LZL004)(to M.Y.)Program of Science and Technology for the youth innovation team in universities of Shandong Province(2020KJL001)(to M.Y.).
文摘Epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective targeted therapy drugs for advanced nonsmall cell lung cancer(NSCLC)patients carrying sensitized EGFR mutations.The rapid development of EGFR-TKIs resistance represents a major clinical challenge for managing NSCLC.The chromosome 4q12 is the first genome-wide association study(GWAS)-reported locus associated with progression-free survival(PFS)of NSCLC patients treated with EGFR-TKIs.However,the biological significance of the noncoding transcripts at 4q12 in NSCLC remains elusive.In the present study,we identified two 4q12 long noncoding RNAs(lncRNAs)LCETRL3 and LCETRL4 which could significantly dimmish EGFR-TKIs efficiency.In line with their oncogenic role,evidently higher LCETRL3 and LCETRL4 levels were observed in NSCLC tissues as compared with normal specimens.Importantly,lncRNA LCETRL3 can interact with oncoprotein TDP43 and inhibit ubiquitination and degradation of TDP43.Similarly,lncRNA LCETRL4 can bind and stabilize oncoprotein EIF2S1 through reducing ubiquitin-proteasome degradation of EIF2S1.In particular,elevated levels of LCETRL3 or LCETRL4 in NSCLC cells resulted in stabilization of TDP43 or EIF2S1,increased levels of NOTCH1 or phosphorylated PDK1,activated AKT signaling and,thus,EGFR-TKIs resistance.Taken together,our data revealed a novel model that integrates two lncRNAs transcribed from the 4q12 locus into the regulation of EGFR-TKIs resistance in NSCLC.These findings shed new light on the importance of functionally annotating lncRNAs in the GWAS loci and provided insights to declare novel druggable targets,i.e.,lncRNAs,which may unlock the therapeutic potential of EGFR-TKIs resistant NSCLC in the clinic.
基金supported by funds fromtheNationalNatural Science Foundation of China(82030082)the Academic Promotion Program of Shandong First Medical University(2019ZL002)+3 种基金the Radiation Oncology Innovate Unit,Chinese Academy of Medical Sciences(2019RU071)Key Research and Development Project of Shandong Province of China(2021CXGC011102)Shandong Provincial Natural Science Foundation(ZR2021QH006)Beijing Bethune Charitable Foundation(flzh202118).
文摘Dear Editor,Increasing numbers of studies have revealed the immunomodulating effects of radiotherapy when combined with immune checkpoint inhibitors,as radioimmunotherapy has proven to be a promising treatment[1].Radioimmunotherapy has shown significantly improved tumor responses than radiotherapy or immunotherapy alone in various malignant tumors[2–4].It has also been applied to cervical cancer in multiple ongoing clinical trials(NCT03612791[5]and NCT02635360[6]).However,tumor recurrence andmetastasis are often unavoidable.As such,investigations into radioimmunotherapy-induced tumor ecosystem evolution are essential for guiding improvements in treatment strategies that achieve better long-term disease control.To date,several studies have investigated radiochemotherapy-induced tumor ecosystem evolution using bulk RNA-sequencing and immune staining[7,8].However,these findings were limited owing to the cellular heterogeneity in cancers.Single-cell RNA-sequencing(scRNA-seq)enables the characterization of cell compositions and transcriptomic states in the tumor at single-cell resolution.
