In-Depth Genomic Characterization of Programmed Cell Death Ligand 1 (PD-L1) Expression in Chinese Lung Adenocarcinoma Patients

Background: Immune checkpoint blockades have revolutionized anticancer treatments for lung cancers, and PD-L1 expression has been served as crucial predictive biomarkers for immunotherapies. However, PD-L1 expression has been found to be influenced by some extrinsic or intrinsic factors in vitro or to be associated with other biomarkers in vivo. Methods: A amount of tumor tissues was taken from a biopsy or surgery for PD-L1 expression assay and genomic profiling in Chinese lung adenocarcinoma patients. In-depth retrospective analyses of clinical features, gene alternations, singling pathways and immune signatures was conducted in negative group (TPS < 1%), intermediate group (1% ≤ TPS < 50%), and high group (TPS ≥ 50%). Clinical responses to selected mutation were also evaluated from public database such as TCGA and MSKCC.Results: A total of 248 Chinese patients with lung adenocarcinoma was retrospectively identified and included in this study, consisting of negative group (n=124, 50%), intermediate group (n=93, 38%), and high group (n=38, 12%). High tumor mutation burden was significantly as associated with high PD-L1 expression. In addition, PD-L1 expression was highly related with gene alternations such as PRKDC, KMT2D, ERBB2 and SETD2. Moreover, signaling pathways of DDR, TP53, cell cycles and NOTCH also obviously related with PD-L1 expression. Besides, most of patients in high PD-L1 group were determined as high-grade immune subtypes (C2-C4), showing significant higher levels of IFN-gamma, CD8+ T-cells, NK cells, NK CD56 dim cells, Th1 cells, Th2 cells (P < 0.0001). Moreover, the prognostic value of SETD2 mutation was slight positive with overall survival from MSKCC cohort (HR 1.92 [95%CI 0.90-4.10], P =0.085), and the percentage of IFN-gamma was significantly higher in SETD2 mutant group than in wild-type subgroup (P < 0.01).Conclusions: This study illustrated in-depth genomic profiles and immune signatures of PD-L1 expression in Chinese lung adenocarcinoma patients, which might interpret more potential molecular mechanisms for anti-cancer immunotherapy in NSCLC.