Department of Medical Oncology, the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital); Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410022, China.
Cell Death Dis. 2022 Dec 21;13(12):1064. doi: 10.1038/s41419-022-05510-4.
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 cytotoxicity gene expression signatures and immune suppressive features, and similar ICI-response-related biomarkers to WT NSCLC. A similar TIME pattern was observed between the BRAF V600E and Non-V600E subgroups of NSCLC. The 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 support that BRAF mutation did not modulate TIME in NSCLC and therapeutic responses to ICIs. Patients with NSCLC harboring BRAF mutation should not be denied treatment with ICIs.
先前的小规模研究报告称，BRAF 突变的 NSCLC 患者对免疫检查点抑制剂（ICI）具有相当的敏感性。然而，BRAF 突变如何影响肿瘤免疫微环境（TIME）尚不清楚。我们对 57 例 BRAF 突变和野生型（WT）NSCLC 标本（队列 A）进行了 Nanostring-panel RNA 测序，以评估 TIME。我们在 417 例 WT 和 BRAF 突变的 NSCLC 患者（队列 B）中确定了 ICI 单药或联合治疗的疗效。我们发现，BRAF 突变肿瘤的 CD8+T 细胞与 Tregs 的比例、细胞毒性基因表达特征和免疫抑制特征的平衡以及与 WT NSCLC 相关的 ICI 反应生物标志物相似。在 NSCLC 的 BRAF V600E 和非 V600E 亚组之间观察到类似的 TIME 模式。进一步的回顾性研究证实，ICI 单药或联合治疗导致 WT（n=358）和 BRAF 突变（n=59）NSCLC 患者的总生存期（OS）（HR：0.85；95%CI，0.56 至 1.30；p=0.47）和无进展生存期（PFS）（HR：1.02；95%CI，0.72 至 1.44；p=0.91）相似。同样，BRAF V600E 或非 V600E NSCLC 患者对免疫治疗的反应也相似。我们的研究结果表明，BRAF 突变并未调节 NSCLC 中的 TIME，以及对 ICI 的治疗反应。不应拒绝携带 BRAF 突变的 NSCLC 患者接受 ICI 治疗。
