The genomic landscape of immune-related genes and its correlations with TMB and PD-L1 expression in Chinese NSCLC.

Abstract

e21056 Background: Understanding the genomic landscape of immune-related genes (IRGs) of patient with Non-Small Cell Lung Carcinoma (NSCLC) may provide critical insight and facilitate development of novel strategies for cancer therapy. Methods: Targeted next generation sequencing (NGS) was performed on tissue obtained from patients with NSCLC using a 381-gene panel. The IRGs were mainly based on a published article that summarized the genes related to activated T cells, immune cytolytic activity and IFN-γ release. Genomic alterations including single nucleotide variation (SNV), insertions/deletions, copy number variations (CNV) and gene fusions were assessed. Mutational profiles of IRGs and its correlations with Tumor mutation burden (TMB) and PD-L1 expression in NSCLC patients were analyzed from the 3D Medicine database. Results: Genomic data of 2,510 patients with NSCLC were analyzed via tissue detection [median age 62 years, (IQR: 54 - 69 years)]. 4.26% (107 / 2,510) of the patients had at least one characterized altered IRGs. The most frequently mutated IRGs identified for all genomic alternations occurred in PDCD1LG2 (40%), FAS (27%), LCK (23%), CD274 (21%), CD74 (3%), and missense mutations were the mainly mutant types of PDCD1LG2 and LCK, and copy number gains were showed in PDCD1LG2 and CD274. TMB levels in NSCLC patients with IRGs mutations were higher than in wild-type patients (mean TMB: 14.17 mut/MB vs 9.27 mut/MB, P < 0.001). 65.42% (70/107, 9.35% for PD-L1 > = 1% and < 5%, 28.97% for PD-L1 > = 5% and < 50%, 27.10% for PD-L1 > = 50%) of patients harboring PD-L1-positive ( > = 1%), and the proportion of patients with mutations in IRGs does not exceed 10% in each subgroup. Results of Pearson Chi-square test showed that the PD-L1 expression had different between two groups ( Χ2 = 13.3774, P = 0.0038), patients harboring IRGs mutation had a significantly higher level of PD-L1 than those wide-type patients (P = 0.001). Conclusions: Genomic landscape of IRGs significantly correlated with that of PD-L1 expression. Further analyses using more precisely IRGs and different stage NSCLC samples are requisite to support a role for IRGs as an target to immune therapy of cancers.