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

• DOI: 10.1136/jitc-2021-003773
• Publication Date: 2021-12-09T16:38:56Z
• Authors: 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
• Keywords: Infiltration (HVAC); Primary (astronomy)

Diagnosing and treating patients with multiple primary lung cancers (MPLCs) bring challenges to the clinic, preliminary evidence has revealed unsatisfying outcomes after targeted therapy immunotherapy. Therefore, we surveyed genomic profiles of MPLCs their possible associations tumor mutation burden (TMB), programmed death-ligand 1 (PD-L1), immune cell infiltration landscape.A total 112 surgically resected 294 tumors were eligible, 255 sequenced using a 1021-gene panel. Immunohistochemistry staining was performed evaluate levels PD-L1 density CD3+/CD8+ tumor-infiltrating lymphocytes (TILs), CD68+/CD163+ tumor-associated macrophages (TAMs) at central invasive margin, immunotypes generated based on those variables.MPLCs often occur simultaneously in non-smoker women younger than 60 years manifest as ground-glass opacities, adenocarcinoma, stage I lesions. The most frequently mutated genes EGFR (56%), ERBB2 (12%), TP53 BRAF (11%), RBM10 KRAS (9%). We found 87 (77.7%) diverse profiles, 61 (54.5%) who shared least one putative driver gene between different presented more aggressive tumors. median TMB 1.92 mutations/Mb, high-TMB (≥3) lesions harbored EGFRL858R/KRASG12C/RBM10/TP53/LRP1B mutations or wild-type ERBB2. Only 8.1% 3.9% positive for cells, this positivity frequent LRP1B/TP53-mutant EGFRL858R/RBM10/TP53 positively associated specific cells an inflamed immunotype, but negatively correlated. TMB, CD3+TILs, TAMs significant heterogeneity among paired (all kappa <0.2), CD8 +TILs uniformly present pairs.MPLCs are driven by molecular events exhibit low PD-L1, heterogeneous landscape. Specific microenvironmental landscape MPLCs. Our findings can help guide diagnoses identify patient populations that may benefit from immunotherapy therapy.