Abstract 6117: Clinical and Molecular Correlates of Immune Marker Profiling and PD-L1 Expression in Non-Small Cell Lung Cancer

Abstract Background: Understanding the genomic landscape and tumor immune microenvironment of non-small cell lung cancer (NSCLC) may provide critical insight into the biology of tumor immune response and novel strategies for overcoming immunotherapy resistance. The association of clinical and genomic features with tumor immune microenvironment in NSCLC patients remains unclear. Methods: In this retrospective cohort study, we profiled PD-L1 and immune cell marker expressions and performed targeted next-generation sequencing (Geneseeq Technology Inc., Nanjing) of baseline tissue samples from 100 NSCLC patients. The levels of CD8+, CD68+ and HLA-DR+ immune cells were assessed by multiplexed immunohistochemistry (mIHC) assay. Immune microenvironment markers and PD-L1 expression was analyzed for associations with clinical features and mutations at both the single gene and pathway levels. Results: Mutations in TP53, SETD2, RET and the p53 signaling pathway were significantly associated with high PD-L1 high expression (P<0.001; P=0.002; P=0.04; P=0.001, respectively). Patients with high PD-L1 expression showed a trend towards higher stromal CD8+ lymphocytes (P=0.1), Alterations in T cell and B cell pathways were also associated with increased stromal CD8+ T cells (P=0.03 and P=0.08, respectively). The infiltration of intratumoral CD68(+)HLA-DR(+) M1-like macrophages positively correlated with high PD-L1 high expression (P=0.07), Hippo pathway alterations (P=0.06). By contrast, the levels of intratumoral M1-like macrophages negatively correlated with alterations in the NRF2/KEAP1 pathway (P=0.005), which might account for the poor immunotherapy outcome in this subset of patients. Conclusions: Our study demonstrates the complex relationship between gene mutations and aberrations in signaling pathways with the immune microenvironment in NSCLC. Specific molecular features are associated with unique immune profiles and may impact the response to immune checkpoint inhibitors. Citation Format: Yunfei Shi, Youming Lei, Yinqiang Liu, Jin Duan, Wei Zhao, Fujun Zhang, Guoli Lv, Qian Wu, Mengmeng Wu, Jiani C. Yin, Yang Shao. Clinical and molecular correlates of immune marker profiling and PD-L1 expression in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6117.