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Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy

引用

Cancer Communications 2022年第12期42卷 1331-1346页

作者： Fengying Wu Tao Jiang Gongyan Chen Yunchao Huang Jianying Zhou Lizhu Lin Jifeng Feng Zhehai Wang Yongqian Shu Jianhua Shi Yi Hu Qiming Wang Ying Cheng Jianhua Chen Xiaoyan Lin Yongsheng Wang Jianan Huang Jiuwei Cui Lejie Cao Yunpeng Liu Yiping Zhang Yueyin Pan Jun Zhao LiPing Wang Jianhua Chang Qun Chen Xiubao Ren Wei Zhang Yun Fan Zhiyong He Jian Fang Kangsheng Gu Xiaorong Dong Tao Zhang Wei Shi Jianjun Zou Xuejuan Bai Shengxiang Ren Caicun Zhou Department of Thoracic Medical Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433P.R.China Department of Respiratory Medicine Harbin Medical University Cancer HospitalHarbinHeilongjiang 150000P.R.China Department of Thoracic Surgery Oncology Yunnan Cancer Hospital&The Third Affiliated Hospital of Kunming Medical University&Yunnan Cancer CenterKunmingYunnan 650118P.R.China Department of Respiratory Medicine The First Affiliated Hospital of Zhejiang UniversityHangzhouZhejiang 310009P.R.China Department of Oncology Center The First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouGuangdong 510405P.R.China Department of Thoracic Medical Oncology Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingJiangsu 210009P.R.China Department of Respiratory Shandong Cancer Hospital&InstituteJinanShandong 250117P.R.China Department of Oncology Jiangsu Province HospitalNanjingJiangsu 210000P.R.China Department of Medical Oncology Linyi Cancer HospitalLinyiShandong 276000P.R.China Department of Oncology Chinese PLA General HospitalBeijing 100853P.R.China Department of Respiratory Medicine Henan Cancer HospitalZhengzhouHenan 450000P.R.China Department of Thoracic Oncology Jilin Cancer HospitalChangchunJilin 130012P.R.China Department of Medical Oncology-Chest Hunan Cancer HospitalChangshaHunan 410006P.R.China Department of Oncology Fujian Medical University Union HospitalFuzhouFujian 350001P.R.China Department of Thoracic Medical Oncology West China HospitalSichuan UniversityChengduSichuan 610000P.R.China Department of Respiration First Affiliated Hospital of Suzhou UniversitySuzhouJiangsu 215002P.R.China Department of Medical Oncology The First Bethune Hospital of Jilin UniversityChangchunJilin 130021P.R.China Pulmonary and Critical Care Medicine The First Affiliated Hospital University of Science Technology of ChinaHefeiAnhui 230036P.R.China De

Background:Although programmed cell death 1(PD-1)blockade plus chemotherapy can significantly prolong the progression-free survival(PFS)and overall survival(OS)in first-line settings in patients with driver-negative advanced non-small-cell lung cancer(NSCLC),the predictive biomarkers remain ***,we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus ***:Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy *** immune microenvironmental markers,including PD-1 ligand(PDL1),CD8,CD68,CD4 and forkhead box P3,were assessed using multiplex immunofluorescence(mIF)***-Meier curveswere used to determine treatment outcome differences according to their expression *** profiles were compared between tumors with distinct expression levels of these markers and their ***:Responders had significantly higher CD8/PD-L1(P=0.015)or CD68/PD-L1 co-expression levels(P=0.021)than non-responders in the camrelizumab plus chemotherapy group,while no difference was observed in the chemotherapy *** with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS(P=0.002,P=0.024;respectively)and OS(P=0.006,P=0.026;respectively)than those with low co-expression in camrelizumab plus chemotherapy *** comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification,significantly better PFS(P=0.003)and OS(P=0.032)were observed in high co-expression *** predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological *** the prevalence of TP53 or KRAS mutations was similar bet

关键词： Non-small-cell lung cancer PD-1 CD8 CD68 tumor immune microenvironment

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