Previous small size studies reported BRAF mutated NSCLC patients have comparable sensitivity to immune checkpoint inhibitors (ICIs). However, how BRAF mutation affects the tumor immune microenvironment (TIME) is unknown.
We performed Nanostring-panel RNA sequencing to evaluate TIME in 57 BRAF mutated and wild-type (WT) NSCLC specimens (cohort A). The efficacy of ICI monotherapy or combined therapies was determined in 417 patients with WT and BRAF mutated NSCLC (cohort B).
We found that BRAF-mutant tumors had similar ratios of CD8+ T cells to Tregs, the balance of a cytotoxicity gene expression signatures and immune suppressive features, and similar ICI-response-related biomarkers to WT NSCLC. A similar pattern of TIME was observed between the BRAF V600E and non-V600E subgroups of NSCLC. Further retrospective study confirmed that treatment with ICI monotherapy or combined therapies resulted in similar overall survival (OS) ( (HR: 0.85; 95% CI, 0.56 to 1.30; p=0.47) and progress-free survival (PFS) (HR: 1.02; 95% CI, 0.72 to 1.44; p=0.91) of patients with WT (n = 358) and BRAF mutant (n=59) NSCLC. Similarly, both patients with BRAF V600E or non-V600E NSCLC had similar responses to immunotherapy.
Our findings indicated that BRAF mutation, including V600 E, did not modulate TIME in NSCLC and therapeutic responses to ICIs. Keywords: BRAF; NSCLC; TIME; immunotherapy.
The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital).
This work was supported by Beijing Xisike Clinical Oncology Research Foundation (Grant No. Y-XD202002-0251), the National Natural Science Foundation of China (Grant No. 81972718), the Natural Science Foundation of Zhejiang Province (Grant No. LY22H160037) and the Science and Technology Program for Health and Medicine in Zhejiang Province, China (Gran No. 2021KY541).
All authors have declared no conflicts of interest.