In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-r...In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8^(+) T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.展开更多
In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer(NK) cells, which are an important subset of innate lymphoc...In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer(NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment(TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.展开更多
Advances in chimeric antigen receptor(CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies.However,progress is still hindered as clinical b...Advances in chimeric antigen receptor(CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies.However,progress is still hindered as clinical benefit is only available for a fraction of patients.A lack of understanding of CAR-T cell behaviors in vivo at the single-cell level impedes their more extensive application in clinical practice.Mounting evidence suggests that single-cell sequencing techniques can help perfect the receptor design,guide gene-based T cell modification,and optimize the CAR-T manufacturing conditions,and all of them are essential for long-term immunosurveillance and more favorable clinical outcomes.The information generated by employing these methods also potentially informs our understanding of the numerous complex factors that dictate therapeutic efficacy and toxicities.In this review,we discuss the reasons why CAR-T immunotherapy fails in clinical practice and what this field has learned since the milestone of single-cell sequencing technologies.We further outline recent advances in the application of single-cell analyses in CAR-T immunotherapy.Specifically,we provide an overview of single-cell studies focusing on target antigens,CAR-transgene integration,and preclinical research and clinical applications,and then discuss how it will affect the future of CAR-T cell therapy.展开更多
Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a ca...Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.展开更多
Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq dat...Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.展开更多
Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Me...Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.展开更多
Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advance...Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advanced GC.In recent years,with the progress in tumor immunology research,attention has shifted toward immunotherapy as a therapeutic approach for GC.Programmed cell death protein 1(PD-1)inhibitors,as novel immunosuppressive medications,have been widely utilized in the treatment of GC.However,many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy.To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy,to maximize the clinical activity of immunosuppressive drugs,and to elicit a lasting immune response,it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients.This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment,aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.展开更多
Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help ...Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.展开更多
Lung infections are usually caused by pathogenic microorganisms and are a disease with high morbidity and mortality. In clinical practice, the use of broad-spectrum antibiotics has become increasingly common, but this...Lung infections are usually caused by pathogenic microorganisms and are a disease with high morbidity and mortality. In clinical practice, the use of broad-spectrum antibiotics has become increasingly common, but this has also led to the problem of antibiotic abuse and irrational use, which in turn has spawned the emergence of multidrug-resistant bacteria, making the treatment of lung infections more complex and difficult. In the human immune system, γδ T cells play a crucial role in defense against foreign pathogens and regulation of autoimmune responses. These cells act as a bridge between innate and adaptive immunity and can be rapidly activated in the early stages of infection to produce inflammatory factors and chemokines that attract other immune cells to the site of infection. Recent advances have shown that γδ T cells not only play a direct role in the innate immunity of pathogen infection, but are also involved in regulating the subsequent adaptive immune response. The aim of this review is to explore the mechanism of γδ T cells in lung infections and to summarize the current progress of clinical research, with the aim of providing new scientific basis and therapeutic strategies for the treatment of lung infections.展开更多
In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunct...In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunction, loss of proliferation ability, and sustained high expression of a variety of inhibitory receptors, with metabolic and epigenetic changes. Tex cells are heterogeneous, including several subsets with different characteristics at different stages of differentiation. Immune checkpoint inhibitors (ICIs) can restore the effect or function of Tex cells, indicating that this T cell subset plays a key role in tumor immunotherapy. The understanding of the mechanism of CD8<sup>+</sup> T cell exhaustion will be helpful to the implementation of tumor immunotherapy. This article reviews the production, differentiation and functional characteristics of Tex cells and their relationship with tumor immunotherapy.展开更多
In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made breakthroughs in the treatment of hematological tumors. However, due to the different characteristics of solid tumors from hematological tumor...In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made breakthroughs in the treatment of hematological tumors. However, due to the different characteristics of solid tumors from hematological tumors, CAR-T has not achieved good efficacy in the treatment of solid tumors. The key factors limiting the efficacy of CAR-T mainly include the solid tumor cells themselves and their special tumor microenvironment (TME), which damage CAR-T function in multiple processes such as CAR-T infiltration to tumor tissue sites, CAR-T maintaining anti-tumor activity in TME, and target recognition and killing of tumor cells by CAR-T. To solve these problems, more and more preclinical studies have proposed potentially effective solutions, and corresponding clinical studies have been carried out one after another. In this article, the existing challenges and corresponding optimization strategies of CAR-T cell therapy for solid tumors will be reviewed, to provide a reference for the future exploration of CAR-T therapy.展开更多
Cancer is a potentially life-threatening disease characterized by the immortalization of tumor cells in the host. Immunotherapy has recently gained increasing interest among researchers due to its tremendous potential...Cancer is a potentially life-threatening disease characterized by the immortalization of tumor cells in the host. Immunotherapy has recently gained increasing interest among researchers due to its tremendous potential for preventing tumor progression and metastasis. Regulatory T cells (Tregs) are a subgroup of suppressive CD4^+ T cells that play a vital role in the maintenance of host immune homeostasis. Treg deficiency can induce severe autoimmune, hypersensitivity, and auto-inflammatory disorders, among other diseases. Tregs are commonly enriched in a tumor microenvironment, and a greater number of immune-suppressive Tregs often indicates a poorer prognosis;therefore, there is renewed interest in the function of Tregs and in their clinical application in antitumor immunotherapy. Accumulating strategies that focus on the depletion of Tregs have appeared to be effective in antitumor immunity. It is expected that Treg-targeting strategies will provide great opportunities for improving antitumor efficiency in combination with other therapeutics (e.g., chimeric antigen receptor T cell (CAR-T)-based cell therapy or immune checkpoint blockading).展开更多
Due to the unique features of innate immune cells, the role of γδT cells in tumor immunity has gradually attracted more and more attention. Previous studies have found that γδT cells play a dual role in tumor immu...Due to the unique features of innate immune cells, the role of γδT cells in tumor immunity has gradually attracted more and more attention. Previous studies have found that γδT cells play a dual role in tumor immunology: tumor-promoting and tumor-controlling.The anti-tumor therapy of γδT cells has made remarkable success in clinical application. Especially in recent years, researchers have provided some novel effective ways such as γδT cells exosomes and adoptive chimeric antigen receptor-γδT cells immunotherapy. However, some problems remain to be solved, such as low expansion rate, poor targeting, and tumor microenvironment limiting the effectiveness of γδT immunotherapy. Traditional Chinese medicine is expected to play a positive role in the body immune-enhancing function, promoting the proliferation and activation of γδT cells, and inducing the differentiation ofγδT cells. In this review, we summarize the recent research progress and urgent problems of γδT cells in anti-tumor immunotherapy. Moreover, some new strategies of γδT cells for tumor immunotherapy were proposed.展开更多
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac...Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.展开更多
As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic...As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.展开更多
Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been id...Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.展开更多
Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens gener...Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells,making them an attractive therapeutic target.Currently,neoantigens find utility in various domains,primarily in the realm of neoantigen vaccines such as DC vaccines,nucleic acid vaccines,and synthetic long peptide vaccines.Additionally,they hold promise in adoptive cell therapy,encompassing tumor-infiltrating cells,T cell receptors,and chimeric antigen receptors which are expressed by genetically modified T cells.In this review,we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens,discussed the potential of neoantigen burden as an immune checkpoint in clinical settings.With the aid of state-of-the-art sequencing and bioinformatics technologies,together with significant advancements in artificial intelligence,we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy,from screening to clinical application.展开更多
Objective To investigate the effect of dendritic cells pulsed with brain tumor stem cells which are used to treat on intracranial glioma. Methods We obtained murine brain tumor stem cells by grow ing C6 cells in epide...Objective To investigate the effect of dendritic cells pulsed with brain tumor stem cells which are used to treat on intracranial glioma. Methods We obtained murine brain tumor stem cells by grow ing C6 cells in epidermal grow th factor/basic fibroblast grow th factor w ithout serum.Dendritic cells isolated from rat bone marrow w ere pulsed w ith BTSCs. Rat brain展开更多
Traditional treatments against advanced non-small cell lung cancer(NSCLC)with high morbidity and mortality continue to be dissatisfactory.Given this situation,there is an urgent requirement for alternative modalities ...Traditional treatments against advanced non-small cell lung cancer(NSCLC)with high morbidity and mortality continue to be dissatisfactory.Given this situation,there is an urgent requirement for alternative modalities that provide lower invasiveness,superior clinical effectiveness,and minimal adverse effects.The combination of photodynamic therapy(PDT)and immunotherapy gradually become a promising approach for high-grade malignant NSCLC.Nevertheless,owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment(TME),the efficacy of this combination therapy approach is less than ideal.In this study,we construct a novel nanoplatform that indocyanine green(ICG),a photosensitizer,loads into hollow manganese dioxide(MnO2)nanospheres(NPs)(ICG@MnO2),and then encapsulated in PD-L1 monoclonal antibodies(anti-PD-L1)reprogrammed exosomes(named ICG@MnO2@Exo-anti-PD-L1),to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities.The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME,thereby activating T cell response.Subsequently,upon endocytic uptake by cancer cells,MnO2 catalyzes the conversion of H2O2 to O2,thereby alleviating tumor hypoxia.Meanwhile,ICG further utilizes O2 to produce singlet oxygen(1O2)to kill tumor cells under 808 nm near-infrared(NIR)irradiation.Furthermore,a high level of intratumoral H2O2 reduces MnO2 to Mn2+,which remodels the immune microenvironment by polarizing macrophages from M2 to M1,further driving T cells.Taken together,the current study suggests that the ICG@MnO2@Exo-anti-PDL1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.展开更多
Bladder cancer(BC)is the 10th most common cancer worldwide,with about 0.5 million reported new cases and about 0.2 million deaths per year.In this scoping review,we summarize the current evidence regarding the clinica...Bladder cancer(BC)is the 10th most common cancer worldwide,with about 0.5 million reported new cases and about 0.2 million deaths per year.In this scoping review,we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines.We searched PubMed,CENTRAL,Embase,and supplemented with manual searches through the Scopus,and Web of Science for published studies until February 2023.We included original studies that used at least one single-cell technology to study bladder cancer.Forty-one publications were included in the review.Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy.Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples.The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level.Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management.This nascent tool can advance the early diagnosis,prognosis judgment,and targeted therapy of bladder cancer.展开更多
基金supported by grants from the National Natural Science Foundation of China (Grant No. 32270955)the Jiangsu Provincial Medical Key Discipline (Grant No. YXZDXK202236)+1 种基金the Key Project of Jiangsu Provincial Health Commission (Grant No. K2023069)the Science and Technology Support Plan (Social Development) Project of Changzhou (Grant No. CE20235058)。
文摘In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8^(+) T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.
文摘In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer(NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment(TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.
基金National Key Research and Development Program of China(2022YFC2502700)National Natural Science Foundation of China(8187343482100190).
文摘Advances in chimeric antigen receptor(CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies.However,progress is still hindered as clinical benefit is only available for a fraction of patients.A lack of understanding of CAR-T cell behaviors in vivo at the single-cell level impedes their more extensive application in clinical practice.Mounting evidence suggests that single-cell sequencing techniques can help perfect the receptor design,guide gene-based T cell modification,and optimize the CAR-T manufacturing conditions,and all of them are essential for long-term immunosurveillance and more favorable clinical outcomes.The information generated by employing these methods also potentially informs our understanding of the numerous complex factors that dictate therapeutic efficacy and toxicities.In this review,we discuss the reasons why CAR-T immunotherapy fails in clinical practice and what this field has learned since the milestone of single-cell sequencing technologies.We further outline recent advances in the application of single-cell analyses in CAR-T immunotherapy.Specifically,we provide an overview of single-cell studies focusing on target antigens,CAR-transgene integration,and preclinical research and clinical applications,and then discuss how it will affect the future of CAR-T cell therapy.
基金was supported by National Natural Science Foundation of China(81972893,82172719)Natural Science Foundation of Henan(212300410071)Training program for young key teachers in Henan Province(2020GGJS019).
文摘Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.
基金Liuzhou City's Top Ten Hundred Talents Project,Liuzhou Science and Technology Project(Grant Nos.2021CBC0126 and 2021CBC0123)Guangxi Zhuang Autonomous Region Health and Family Planning Commission Projects(Z20210561,Z20210903)+1 种基金liuzhou Scienceand Technology Plan Projects(2021CBC0121,2021CBC0128).
文摘Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.
基金supported by the National Natural Science Foundation of China(No.81972681,82103677)Tianjin Education Commission Research Plan Project(No.2021KJ201)+1 种基金Shenzhen High-level Hospital Construction Fund(No.G2022139)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-009A).
文摘Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.
基金Natural Science Foundation of Gansu Province,No.21JR1RA186and the Health Industry Research Program of Gansu Province,No.GSWSKY2021-043.
文摘Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advanced GC.In recent years,with the progress in tumor immunology research,attention has shifted toward immunotherapy as a therapeutic approach for GC.Programmed cell death protein 1(PD-1)inhibitors,as novel immunosuppressive medications,have been widely utilized in the treatment of GC.However,many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy.To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy,to maximize the clinical activity of immunosuppressive drugs,and to elicit a lasting immune response,it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients.This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment,aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.
文摘Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.
文摘Lung infections are usually caused by pathogenic microorganisms and are a disease with high morbidity and mortality. In clinical practice, the use of broad-spectrum antibiotics has become increasingly common, but this has also led to the problem of antibiotic abuse and irrational use, which in turn has spawned the emergence of multidrug-resistant bacteria, making the treatment of lung infections more complex and difficult. In the human immune system, γδ T cells play a crucial role in defense against foreign pathogens and regulation of autoimmune responses. These cells act as a bridge between innate and adaptive immunity and can be rapidly activated in the early stages of infection to produce inflammatory factors and chemokines that attract other immune cells to the site of infection. Recent advances have shown that γδ T cells not only play a direct role in the innate immunity of pathogen infection, but are also involved in regulating the subsequent adaptive immune response. The aim of this review is to explore the mechanism of γδ T cells in lung infections and to summarize the current progress of clinical research, with the aim of providing new scientific basis and therapeutic strategies for the treatment of lung infections.
文摘In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunction, loss of proliferation ability, and sustained high expression of a variety of inhibitory receptors, with metabolic and epigenetic changes. Tex cells are heterogeneous, including several subsets with different characteristics at different stages of differentiation. Immune checkpoint inhibitors (ICIs) can restore the effect or function of Tex cells, indicating that this T cell subset plays a key role in tumor immunotherapy. The understanding of the mechanism of CD8<sup>+</sup> T cell exhaustion will be helpful to the implementation of tumor immunotherapy. This article reviews the production, differentiation and functional characteristics of Tex cells and their relationship with tumor immunotherapy.
文摘In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made breakthroughs in the treatment of hematological tumors. However, due to the different characteristics of solid tumors from hematological tumors, CAR-T has not achieved good efficacy in the treatment of solid tumors. The key factors limiting the efficacy of CAR-T mainly include the solid tumor cells themselves and their special tumor microenvironment (TME), which damage CAR-T function in multiple processes such as CAR-T infiltration to tumor tissue sites, CAR-T maintaining anti-tumor activity in TME, and target recognition and killing of tumor cells by CAR-T. To solve these problems, more and more preclinical studies have proposed potentially effective solutions, and corresponding clinical studies have been carried out one after another. In this article, the existing challenges and corresponding optimization strategies of CAR-T cell therapy for solid tumors will be reviewed, to provide a reference for the future exploration of CAR-T therapy.
文摘Cancer is a potentially life-threatening disease characterized by the immortalization of tumor cells in the host. Immunotherapy has recently gained increasing interest among researchers due to its tremendous potential for preventing tumor progression and metastasis. Regulatory T cells (Tregs) are a subgroup of suppressive CD4^+ T cells that play a vital role in the maintenance of host immune homeostasis. Treg deficiency can induce severe autoimmune, hypersensitivity, and auto-inflammatory disorders, among other diseases. Tregs are commonly enriched in a tumor microenvironment, and a greater number of immune-suppressive Tregs often indicates a poorer prognosis;therefore, there is renewed interest in the function of Tregs and in their clinical application in antitumor immunotherapy. Accumulating strategies that focus on the depletion of Tregs have appeared to be effective in antitumor immunity. It is expected that Treg-targeting strategies will provide great opportunities for improving antitumor efficiency in combination with other therapeutics (e.g., chimeric antigen receptor T cell (CAR-T)-based cell therapy or immune checkpoint blockading).
文摘Due to the unique features of innate immune cells, the role of γδT cells in tumor immunity has gradually attracted more and more attention. Previous studies have found that γδT cells play a dual role in tumor immunology: tumor-promoting and tumor-controlling.The anti-tumor therapy of γδT cells has made remarkable success in clinical application. Especially in recent years, researchers have provided some novel effective ways such as γδT cells exosomes and adoptive chimeric antigen receptor-γδT cells immunotherapy. However, some problems remain to be solved, such as low expansion rate, poor targeting, and tumor microenvironment limiting the effectiveness of γδT immunotherapy. Traditional Chinese medicine is expected to play a positive role in the body immune-enhancing function, promoting the proliferation and activation of γδT cells, and inducing the differentiation ofγδT cells. In this review, we summarize the recent research progress and urgent problems of γδT cells in anti-tumor immunotherapy. Moreover, some new strategies of γδT cells for tumor immunotherapy were proposed.
文摘Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.
基金Supported by Xi’an Municipal Health Commission of China,No.2022qn07 and No.2023ms11.
文摘As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.
基金the Huzhou Science and Technology Bureau,Zhejiang Province,China(2020GZ41).
文摘Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.
基金This research was supported by the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(No.JNU1AF-CFTP-2022-a01223)Natural Science Foundation of Guangdong Province(2019A1515011763,2020A1515110639,2021A1515010994,2022A1515011695)Guangzhou Science and Technology Plan City-School Joint Funding Project(202201020084,202201020065).
文摘Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells,making them an attractive therapeutic target.Currently,neoantigens find utility in various domains,primarily in the realm of neoantigen vaccines such as DC vaccines,nucleic acid vaccines,and synthetic long peptide vaccines.Additionally,they hold promise in adoptive cell therapy,encompassing tumor-infiltrating cells,T cell receptors,and chimeric antigen receptors which are expressed by genetically modified T cells.In this review,we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens,discussed the potential of neoantigen burden as an immune checkpoint in clinical settings.With the aid of state-of-the-art sequencing and bioinformatics technologies,together with significant advancements in artificial intelligence,we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy,from screening to clinical application.
文摘Objective To investigate the effect of dendritic cells pulsed with brain tumor stem cells which are used to treat on intracranial glioma. Methods We obtained murine brain tumor stem cells by grow ing C6 cells in epidermal grow th factor/basic fibroblast grow th factor w ithout serum.Dendritic cells isolated from rat bone marrow w ere pulsed w ith BTSCs. Rat brain
基金supported by National Natural Science Foundation of China(Grant No.82203310 and No.81972023)Natural Science Foundation of Chongqing City(Grant No.CSTC2021jcyj-msxm0172 and CSTC2022nscq-msx0054)+2 种基金Science and Technology Research Program of Chongqing Municipal Education Commission(Grant No.KJQN202300478)Creative Research Group of CQ University(Grant No.CXQT21017)Program for Youth Innovation in Future Medicine from Chongqing Medical University.
文摘Traditional treatments against advanced non-small cell lung cancer(NSCLC)with high morbidity and mortality continue to be dissatisfactory.Given this situation,there is an urgent requirement for alternative modalities that provide lower invasiveness,superior clinical effectiveness,and minimal adverse effects.The combination of photodynamic therapy(PDT)and immunotherapy gradually become a promising approach for high-grade malignant NSCLC.Nevertheless,owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment(TME),the efficacy of this combination therapy approach is less than ideal.In this study,we construct a novel nanoplatform that indocyanine green(ICG),a photosensitizer,loads into hollow manganese dioxide(MnO2)nanospheres(NPs)(ICG@MnO2),and then encapsulated in PD-L1 monoclonal antibodies(anti-PD-L1)reprogrammed exosomes(named ICG@MnO2@Exo-anti-PD-L1),to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities.The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME,thereby activating T cell response.Subsequently,upon endocytic uptake by cancer cells,MnO2 catalyzes the conversion of H2O2 to O2,thereby alleviating tumor hypoxia.Meanwhile,ICG further utilizes O2 to produce singlet oxygen(1O2)to kill tumor cells under 808 nm near-infrared(NIR)irradiation.Furthermore,a high level of intratumoral H2O2 reduces MnO2 to Mn2+,which remodels the immune microenvironment by polarizing macrophages from M2 to M1,further driving T cells.Taken together,the current study suggests that the ICG@MnO2@Exo-anti-PDL1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.
文摘Bladder cancer(BC)is the 10th most common cancer worldwide,with about 0.5 million reported new cases and about 0.2 million deaths per year.In this scoping review,we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines.We searched PubMed,CENTRAL,Embase,and supplemented with manual searches through the Scopus,and Web of Science for published studies until February 2023.We included original studies that used at least one single-cell technology to study bladder cancer.Forty-one publications were included in the review.Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy.Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples.The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level.Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management.This nascent tool can advance the early diagnosis,prognosis judgment,and targeted therapy of bladder cancer.
