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

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, the CameL Study Group · 发表于：癌症：英文版 · 年份：2022 · DOI：10.1002/cac2.12383 · 被引用次数：20 · 研究领域：Cancer Immunotherapy and Biomarkers、Radiomics and Machine Learning in Medical Imaging、Lung Cancer Diagnosis and Treatment

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 undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy. METHODS: 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 alone. Tumor immune microenvironmental markers, including PD-1 ligand (PD-L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan-Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations. RESULTS: 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 group. Patients 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) an...