Background:For patients with lung cancer,timely identification of new lung lesions as infectious or non-infectious,and accurate identification of pathogens is very important in improving OS of patients.As a new auxiliar...Background:For patients with lung cancer,timely identification of new lung lesions as infectious or non-infectious,and accurate identification of pathogens is very important in improving OS of patients.As a new auxiliary examination,metagenomic next-generation sequencing(mNGS)is believed to be more accurate in diagnosing infectious diseases in patients without underlying diseases,compared with conventional microbial tests(CMTs).We designed this study tofind out whether mNGS has better performance in distinguishing infectious and non-infectious diseases in lung cancer patients using bronchoalveolar lavagefluid(BALF).Materials and Methods:This study was a real-world retrospective review based on electronic medical records of lung cancer patients with bronchoalveolar lavage(BAL)and BALF commercial mNGS testing as part of clinical care from 1 April 2019 through 30 April 2022 at The First Affiliated Hospital of Sun Yat-sen University.164 patients were included in this study.Patients were categorized into the pulmonary non-infectious disease(PNID)group(n=64)and the pulmonary infectious disease(PID)group(n=100)groups based onfinal diagnoses.Results:BALF mNGS increased the sensitivity rate by 60%compared to CMTs(81%vs.21%,p<0.05),whereas there was no significant difference in specificity(75%vs.98.4%,p>0.1).Among the patients with PID,bacteria were the most common cause of infection.Fungal infections occurred in 32%of patients,and Pneumocystis Yersini was most common.Patients with Tyrosine kinase inhibitors(TKIs)therapy possess longer overall survival(OS)than other anti-cancer agents,the difference between TKIs and immuno-checkpoint inhibitors(ICIs)was insignificant(median OS TKIs vs.ICIs vs.Anti-angiogenic vs.Chemo vs.Radiotherapy=76 vs.84 vs.61 vs.58 vs.60).Conclusions:our study indicates that BALF mNGS can add value by improving overall sensitivity in lung cancer patients with potential pulmonary infection,and was outstanding in identifying Pneumocystis infection.It could be able to help physicians adjust the follow-up treatment to avoid the abuse of antibiotics.展开更多
Objective:DNA methylation alterations are early events in carcinogenesis and immune signalling in lung cancer.This study aimed to develop a model based on short stature homeobox 2 gene (SHOX2)/prostaglandin E receptor...Objective:DNA methylation alterations are early events in carcinogenesis and immune signalling in lung cancer.This study aimed to develop a model based on short stature homeobox 2 gene (SHOX2)/prostaglandin E receptor 4gene (PTGER4) DNA methylation in plasma,appearance subtype of pulmonary nodules (PNs) and low-dose computed tomography (LDCT) images to distinguish early-stage lung cancers.Methods:We developed a multimodal prediction model with a training set of 257 individuals.The performance of the multimodal prediction model was further validated in an independent validation set of 42 subjects.In addition,we explored the association between SHOX2/PTGER4 DNA methylation and driver gene mutations in lung cancer based on data from The Cancer Genome Atlas (TCGA) portal.Results:There were significant differences between the early-stage lung cancers and benign groups in the methylation levels.The area under a receiver operator characteristic curve (AUC) of SHOX2 in patients with solid nodules,mixed ground-glass opacity nodules and pure ground-glass opacity nodules were 0.693,0.497 and 0.864,respectively,while the AUCs of PTGER4 were 0.559,0.739 and 0.619,respectively.With the highest AUC of0.894,the novel multimodal prediction model outperformed the Mayo Clinic model (0.519) and LDCT-based deep learning model (0.842) in the independent validation set.Database analysis demonstrated that patients with SHOX2/PTGER4 DNA hypermethylation were enriched in TP53 mutations.Conclusions:The present multimodal prediction model could more efficiently distinguish early-stage lung cancer from benign PNs.A prognostic index based on DNA methylation and lung cancer driver gene alterations may separate the patients into groups with good or poor prognosis.展开更多
CD19 chimeric antigen receptor(CAR)T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia(R/R ALL),but compromising result in chronic lymphoblastic leukemia(CLL)and non-Hodgkin’s l...CD19 chimeric antigen receptor(CAR)T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia(R/R ALL),but compromising result in chronic lymphoblastic leukemia(CLL)and non-Hodgkin’s lymphoma(NHL).CD19-relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome.CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure.Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape.Here,we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen.Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells,suggesting they exhibited dual antigen targeting of CD19 and CD20.By comparing the efficiency of four bispecific CAR modified T cells,it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients’primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model.These data highlighted the potential of loop2019 CAR-T in clinical treatment.展开更多
Dear Editor,Antigen escape is responsible for resistance[1]or disease relapse[2]from single-target chimeric antigen receptor(CAR)-T therapy.Dual-target CAR-T therapy has the potential to overcome the escape problem.Ho...Dear Editor,Antigen escape is responsible for resistance[1]or disease relapse[2]from single-target chimeric antigen receptor(CAR)-T therapy.Dual-target CAR-T therapy has the potential to overcome the escape problem.However,the efficacy and safety assessment of dual-target CAR-T therapy in treating acute myeloid leukemia(AML)need further investigation.Tandem CAR-T therapy has been widely used in research and clinic.However,clustering of two connected single-chain variable fragments(scFvs)[3]and the inappropriate conjugation distance[4]pose a risk of damaging tandem CAR-T cells’function.展开更多
基金This study was funded by Science and Technology Projects in Guangzhou(No.202002030023).
文摘Background:For patients with lung cancer,timely identification of new lung lesions as infectious or non-infectious,and accurate identification of pathogens is very important in improving OS of patients.As a new auxiliary examination,metagenomic next-generation sequencing(mNGS)is believed to be more accurate in diagnosing infectious diseases in patients without underlying diseases,compared with conventional microbial tests(CMTs).We designed this study tofind out whether mNGS has better performance in distinguishing infectious and non-infectious diseases in lung cancer patients using bronchoalveolar lavagefluid(BALF).Materials and Methods:This study was a real-world retrospective review based on electronic medical records of lung cancer patients with bronchoalveolar lavage(BAL)and BALF commercial mNGS testing as part of clinical care from 1 April 2019 through 30 April 2022 at The First Affiliated Hospital of Sun Yat-sen University.164 patients were included in this study.Patients were categorized into the pulmonary non-infectious disease(PNID)group(n=64)and the pulmonary infectious disease(PID)group(n=100)groups based onfinal diagnoses.Results:BALF mNGS increased the sensitivity rate by 60%compared to CMTs(81%vs.21%,p<0.05),whereas there was no significant difference in specificity(75%vs.98.4%,p>0.1).Among the patients with PID,bacteria were the most common cause of infection.Fungal infections occurred in 32%of patients,and Pneumocystis Yersini was most common.Patients with Tyrosine kinase inhibitors(TKIs)therapy possess longer overall survival(OS)than other anti-cancer agents,the difference between TKIs and immuno-checkpoint inhibitors(ICIs)was insignificant(median OS TKIs vs.ICIs vs.Anti-angiogenic vs.Chemo vs.Radiotherapy=76 vs.84 vs.61 vs.58 vs.60).Conclusions:our study indicates that BALF mNGS can add value by improving overall sensitivity in lung cancer patients with potential pulmonary infection,and was outstanding in identifying Pneumocystis infection.It could be able to help physicians adjust the follow-up treatment to avoid the abuse of antibiotics.
基金supported by the National Natural Science Foundation of China(No.81600065 and No.82073805).
文摘Objective:DNA methylation alterations are early events in carcinogenesis and immune signalling in lung cancer.This study aimed to develop a model based on short stature homeobox 2 gene (SHOX2)/prostaglandin E receptor 4gene (PTGER4) DNA methylation in plasma,appearance subtype of pulmonary nodules (PNs) and low-dose computed tomography (LDCT) images to distinguish early-stage lung cancers.Methods:We developed a multimodal prediction model with a training set of 257 individuals.The performance of the multimodal prediction model was further validated in an independent validation set of 42 subjects.In addition,we explored the association between SHOX2/PTGER4 DNA methylation and driver gene mutations in lung cancer based on data from The Cancer Genome Atlas (TCGA) portal.Results:There were significant differences between the early-stage lung cancers and benign groups in the methylation levels.The area under a receiver operator characteristic curve (AUC) of SHOX2 in patients with solid nodules,mixed ground-glass opacity nodules and pure ground-glass opacity nodules were 0.693,0.497 and 0.864,respectively,while the AUCs of PTGER4 were 0.559,0.739 and 0.619,respectively.With the highest AUC of0.894,the novel multimodal prediction model outperformed the Mayo Clinic model (0.519) and LDCT-based deep learning model (0.842) in the independent validation set.Database analysis demonstrated that patients with SHOX2/PTGER4 DNA hypermethylation were enriched in TP53 mutations.Conclusions:The present multimodal prediction model could more efficiently distinguish early-stage lung cancer from benign PNs.A prognostic index based on DNA methylation and lung cancer driver gene alterations may separate the patients into groups with good or poor prognosis.
基金supported by the National Key Research&Development Program of China(2019YFA0110200)the National Natural Science Foundation of China(81830005)+1 种基金the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-041)the Tianjin Applied Fundamental Research Planning Key Project(20JCZDJC00120)。
文摘CD19 chimeric antigen receptor(CAR)T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia(R/R ALL),but compromising result in chronic lymphoblastic leukemia(CLL)and non-Hodgkin’s lymphoma(NHL).CD19-relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome.CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure.Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape.Here,we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen.Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells,suggesting they exhibited dual antigen targeting of CD19 and CD20.By comparing the efficiency of four bispecific CAR modified T cells,it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients’primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model.These data highlighted the potential of loop2019 CAR-T in clinical treatment.
基金supported by the National Key Research and Development Program of China(2021YFC2500300)the National Natural Science Foundation of China(81830005)+1 种基金Haihe Laboratory of Cell Ecosystem Innova-tion Fund(HH22KYZX0032)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2020-I2M-C&T-A-019).
文摘Dear Editor,Antigen escape is responsible for resistance[1]or disease relapse[2]from single-target chimeric antigen receptor(CAR)-T therapy.Dual-target CAR-T therapy has the potential to overcome the escape problem.However,the efficacy and safety assessment of dual-target CAR-T therapy in treating acute myeloid leukemia(AML)need further investigation.Tandem CAR-T therapy has been widely used in research and clinic.However,clustering of two connected single-chain variable fragments(scFvs)[3]and the inappropriate conjugation distance[4]pose a risk of damaging tandem CAR-T cells’function.
