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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trials

文献类型：期刊论文

作者Wang, Jinliang2; Zhou, Wenyong3; Xu, Yu4; Duan, Jianchun5; Zhou, Qiaoxia4; Wang, Guoqiang4; Li, Leo4; Xu, Chunwei6; Wang, Wenxian1; Cai, Shangli4
刊名SCIENCE CHINA-LIFE SCIENCES
出版日期2024-09-12
关键词non-squamous NSCLC squamous NSCLC LRP1B deleterious mutations predictive biomarker immune checkpoint inhibitor
ISSN号1674-7305
DOI10.1007/s11427-023-2554-y
通讯作者Cai, Shangli(shangli.cai@brbiotech.com) ; Wang, Zhijie(wangzj@cicams.ac.cn) ; Wang, Jie(zlhuxi@163.com)
英文摘要In non-small cell lung cancers, the non-squamous and squamous subtypes (nsqNSCLC and sqNSCLC) exhibit disparities in pathophysiology, tumor immunology, and potential genomic correlates affecting responses to immune checkpoint inhibitor (ICI)-based treatments. In our in-house training cohort (n=85), the presence of the LRP1B deleterious mutation (LRP1B-del) was associated with longer and shorter progression-free survival (PFS) on ICIs alone in nsqNSCLCs and sqNSCLCs, respectively (P-interaction=0.008). These results were validated using a larger public ICI cohort (n=208, P-interaction<0.001). Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8(+) T cells in nsqNSCLCs (P=0.040) and sqNSCLCs (P=0.014), respectively. In the POPLAR/OAK cohort, nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel (hazard ratio (HR) =0.70, P=0.046), whereas this benefit was negligible in those without LRP1B-del (HR=1.05, P=0.64). Conversely, sqNSCLCs without LRP1B-del benefited more from atezolizumab (HR=0.60, P=0.002) than those with LRP1B-del (HR=1.30, P=0.31). Consistent results were observed in the in-house CHOICE-01 cohort, in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone (P-interaction=0.008). This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy alone. Our findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs, emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.
WOS关键词CELL LUNG-CANCER ; TISSUE TMB TTMB ; PD-1 BLOCKADE ; OPEN-LABEL ; IMMUNOTHERAPY ; EFFICACY ; ADENOCARCINOMA ; ATEZOLIZUMAB ; MULTICENTER ; EXPRESSION
资助项目National Natural Science Foundation of China[82170108] ; National Natural Science Foundation of China[81700092] ; National Natural Science Foundation of China[81871889] ; National Natural Science Foundation of China[82072586] ; National Natural Science Foundation of China[81630071] ; Clinical Research Projects in Health industry of Shanghai Municipal Health Commission[202340017] ; Foundation of the Center for Medical and Engineering Interdisciplinary Innovation, University of Shanghai for Science and Technology[2023GD-XK08Z] ; Basic Research Foundation of Shanghai Chest Hospital[2020YNJCM05] ; National Key Research and Development Project of China[2022YFC2505004] ; National Key Research and Development Project of China[2022YFC2505000] ; CAMS Innovation Fund for Medical Sciences[2021-1-I2M-012] ; CAMS Key lab of translational research on lung cancer[2018PT31035] ; Beijing Natural Science Foundation[7212084]
WOS研究方向Life Sciences & Biomedicine - Other Topics
语种英语
WOS记录号WOS:001312121400001
出版者SCIENCE PRESS
资助机构National Natural Science Foundation of China ; Clinical Research Projects in Health industry of Shanghai Municipal Health Commission ; Foundation of the Center for Medical and Engineering Interdisciplinary Innovation, University of Shanghai for Science and Technology ; Basic Research Foundation of Shanghai Chest Hospital ; National Key Research and Development Project of China ; CAMS Innovation Fund for Medical Sciences ; CAMS Key lab of translational research on lung cancer ; Beijing Natural Science Foundation
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/135239]  
专题中国科学院合肥物质科学研究院
通讯作者Cai, Shangli; Wang, Zhijie; Wang, Jie
作者单位1.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Dept Clin Trial, Hangzhou 310022, Peoples R China
2.Chinese Peoples Liberat Army Gen Hosp, Dept Oncol, Med Ctr 5, Beijing 100091, Peoples R China
3.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Sch Med, Dept Thorac Surg, Shanghai 200025, Peoples R China
4.Burning Rock Biotech, Guangzhou 510300, Peoples R China
5.Chinese Acad Med Sci & Peking Union Med Coll, CAMS Key Lab Translat Res Lung Canc, State Key Lab Mol Oncol, Dept Med Oncol,Natl Canc Ctr,Natl Clin Res Ctr Can, Beijing 100021, Peoples R China
6.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou 310000, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Jinliang,Zhou, Wenyong,Xu, Yu,et al. Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trials[J]. SCIENCE CHINA-LIFE SCIENCES,2024.
APA Wang, Jinliang.,Zhou, Wenyong.,Xu, Yu.,Duan, Jianchun.,Zhou, Qiaoxia.,...&Wang, Jie.(2024).Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trials.SCIENCE CHINA-LIFE SCIENCES.
MLA Wang, Jinliang,et al."Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trials".SCIENCE CHINA-LIFE SCIENCES (2024).

入库方式： OAI收割

来源：合肥物质科学研究院

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