Tumor immune microenvironment in BRAF V600E mutant lung adenocarcinoma.

Abstract

e21003 Background: The efficacy of immune checkpoint inhibitors (ICIs) is closely related to tumor immune microenvironment (TIME). However, little is known about the role of BRAF V600E mutation in the TIME of lung adenocarcinoma (LUAD). Methods: Here, we analyzed the TIME of LUAD with the BRAF V600E mutation using RNA sequencing and multiplex immunofluorescent (MIF) stained with CD8, CD68, CD163, CD57, PD-1, and PD-L1 antibodies. Patients were divided into the BRAF V600E (n = 31) and driver gene ( ALK, BRAF, EGFR, HER2, KRAS, MET, RET, and ROS1) wild-type groups (WT, n = 32). Results: There were no significant differences between the BRAF V600E and driver gene WT groups in terms of immunological signature scores, including T cell–inflamed gene expression profiles, adhesion molecules, chemokines, cytolytic activity, immunocostimulators, immunoinhibitors, MHC Class I, MHC Class II, MHC Non-Class, IFNg signature, tertiary lymphoid structure, and most of infiltrating immune cell subtypes. MIF showed that the proportions of PD-L1+ cells and CD68-associated tumor-associated macrophages (TAMs) were significantly higher in the BRAF V600E group in the tumor, stroma, and total regions. Notably, the majority of CD68-associated macrophages were CD68+CD163- TAMs. However, the proportions of CD8+, CD8+PD-L1+, and CD8+PD-1+ tumor-infiltrating lymphocytes (Tils) in the BRAF V600E and driver gene WT groups were all comparable in the tumor, stroma, and total region. Conclusions: The TIME was generally similar between the BRAF V600E mutant and driver gene wild-type groups, particularly in the proportion of CD8+ Tils. This may support that BRAF V600E mutation does not affect the efficacy of immune checkpoint inhibitors in LUAD.