Peripheral CD4^(+) T cell signatures in predicting the responses to anti-PD-1/PD-L1 monotherapy for Chinese advanced non-small cell lung cancer

查看全文 作　　者：Liliang [1,2]Xia;Hui [1]Wang;Mingjiao [3]Sun;Yi [1]Yang;Chengcheng [2]Yao;Sheng [4]He;Huangqi [2]Duan;Weimin [2]Xia;Ruiming [2]Sun;Yaxian [1]Yao;Zhiwei [1]Chen;Qiong [5]Zhao;Hong [4]Li;Shun [1]Lu;Ying [2]Wang

机构地区：[1]Department of Shanghai Lung Cancer Center,Shanghai Chest Hospital,Shanghai Jiao Tong University,Shanghai 200030,China;[2]Shanghai Institute of Immunology,Department of Immunology and Microbiology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;[3]Institute of Cancer,Hangzhou Cancer Hospital,Hangzhou 310002,China;[4]Bio-Med Big Data Center,CAS Key Laboratory of Computational Biology,CAS-MPG Partner Institute for Computational Biology,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China;[5]Department of thoracic Oncology,Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College,Hangzhou 310000,China

出　　处：《Science China(Life Sciences)》索引2021年第64卷第10期,共12页

基　　金：supported by the National Key Research and Development Program of China(2016YFC1303303);the National Natural Science Foundation of China(82073152,81802264);Technology Innovation Program of Shanghai(19411950500);Talent Training Program of Shanghai Chest Hospital in 2019,and Incubation Project Plan for Research in Shanghai Chest Hospital(2019YNJCM07)。 摘　　要：Limited benefit population of immune checkpoint inhibitors makes it urgent to screen predictive biomarkers for stratifying the patients.Herein,we have investigated peripheral CD4^(+) T cell signatures in advanced non-small cell lung cancer(NSCLC)patients receiving anti-PD-1/PD-L1 treatments.It was found that the percentages of IFN-γand IL-17A secreting naïve CD4^(+) T cells(Tn),and memory CD4^(+) T cells(Tm)expressing PD-1,PD-L1 and CTLA-4 were significantly higher in responder(R)than non-responder(NonR)NSCLC patients associated with a longer progression free survival(PFS).Logistic regression analysis revealed that the baseline IFN-γ-producing CD4^(+) Tn cells and PD-1^(+)CD4^(+) Tm cells were the most significant signatures with the area under curve(AUC)value reaching 0.849.This was further validated in another anti-PD-1 monotherapy cohort.Conversely,high percentage of CTLA-4^(+)CD4^(+) Tm cells was associated with a shorter PFS in patients receiving anti-PD-L1 monotherapy.Our study therefore elucidates the significance of functional CD4^(+) Tn and Tm subpopulations before the treatment in predicting the responses to anti-PD-1 treatment in Chinese NSCLC patients.The fact that there display distinct CD4^(+) T cell signatures in the prediction to anti-PD-1 and anti-PD-L1 monotherapy from our study provides preliminary evidence on the feasibility of anti-PD-1 and anti-PD-L1 combination therapy for advanced NSCLC patients. 关键词：advanced NSCLC immune checkpoint inhibitors immunotherapy baseline CD4^(+)T cell signatures response prediction

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Peripheral CD4^(+) T cell signatures in predicting the responses to anti-PD-1/PD-L1 monotherapy for Chinese advanced non-small cell lung cancer

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