Genomic profiles and their associations with TMB, PD-L1 expression, and immune cell infiltration landscapes in synchronous multiple primary lung cancers

作者：Chunhong Hu, Lishu Zhao, Wenliang Liu, Songqing Fan, Junqi Liu, Yuxuan Liu, Xiaohan Liu, Long Shu, Xianling Liu, Ping Liu, Chao Deng, Zhenhua Qiu, Chen Chen, Yi Jiang, Qingchun Liang, Lingling Yang, Yang Shao, Qiongzhi He, Danlei Yu, Yue Zeng, Yizheng Li, Yue Pan, Sujuan Zhang, Shenghao Shi, Yurong Peng, Fang Wu · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2021 · DOI：10.1136/jitc-2021-003773 · 被引用次数：79 · 研究领域：Cancer Immunotherapy and Biomarkers、Multiple and Secondary Primary Cancers、Lung Cancer Research Studies

Background Diagnosing and treating patients with multiple primary lung cancers (MPLCs) bring challenges to the clinic, and the preliminary evidence has revealed unsatisfying outcomes after targeted therapy and immunotherapy. Therefore, we surveyed genomic profiles of MPLCs and their possible associations with tumor mutation burden (TMB), programmed death-ligand 1 (PD-L1), and the immune cell infiltration landscape. Materials and methods A total of 112 patients with MPLCs with surgically resected 294 tumors were eligible, and 255 tumors were sequenced using a 1021-gene panel. Immunohistochemistry staining was performed to evaluate the levels of PD-L1 and the density of CD3+/CD8+ tumor-infiltrating lymphocytes (TILs), and CD68+/CD163+ tumor-associated macrophages (TAMs) at the central tumor and invasive margin, and immunotypes were generated based on those variables. Results MPLCs often occur simultaneously in non-smoker women younger than 60 years and manifest as ground-glass opacities, adenocarcinoma, and stage I lung lesions. The most frequently mutated genes in the 255 tumors were EGFR (56%), ERBB2 (12%), TP53 (12%), BRAF (11%), RBM10 (11%), and KRAS (9%). We found 87 (77.7%) patients with diverse genomic profiles, and 61 (54.5%) who shared at least one putative driver gene between different tumors presented more aggressive tumors. The median TMB was 1.92 mutations/Mb, and high-TMB (≥3) lesions often harbored EGFR L858R /KRAS G12C /RBM10/TP53/LRP1B mutations or wild-type ER...