尽管 KRAS 在免疫检查点抑制剂 (ICI) 反应中的预测价值得到公认，但其在该领域的突变的异质行为在很大程度上仍未得到探索。截至目前，尚无研究将 KRAS 亚型变异明确分类为肺癌患者 ICI 反应的独立预后指标。我们分析了 103 名患者的队列，所有患者都携带不同的 KRAS 突变亚型，并用 TCGA 和 GEO 数据库的信息补充了这些数据。我们的研究重点是描绘 KRAS 突变亚型与免疫治疗标志物和免疫细胞组成等因素之间的关系，此外还检查与不同 KRAS 亚型相对应的存活率、药物敏感性和 PD-L1 反应。我们发现 G12V 和 G12D 亚型证明免疫治疗标志物的表达升高，这意味着免疫治疗的潜在益处得到增强。不同 KRAS 突变亚型的初始 B 细胞、激活的 CD4 记忆 T 细胞和调节性 T 细胞 (Treg) 的分布存在显着差异。四种 KRAS 亚型的肿瘤突变负荷 (TMB) 水平存在显着差异，其中 G12D 亚型的 TMB 水平最低。此外，G12C 亚型在无进展间隔 (PFI) 方面表现出最差的预后，与 G12A 亚型相关的更有利的结果形成鲜明对比。我们的研究表明，KRAS 突变在预测接受 ICI 的 LUAD 患者的结果方面表现出相当大的变异性治疗。因此，评估 KRAS 作为 ICI 的生物标志物需要认识到 KRAS 突变固有的潜在多样性。版权所有 © 2023 Wang、Tang、Li、Li 和 Su。

Despite the acknowledged predictive value of KRAS in immune checkpoint inhibitor (ICI) responses, the heterogeneous behavior of its mutations in this sphere remains largely unexplored. As of now, no studies have definitively categorized KRAS subtype variations as independent prognostic indicators for ICI responses in lung cancer patients.We analyzed a cohort of 103 patients, all harboring different KRAS mutation subtypes, and complemented this data with information from TCGA and GEO databases. Our research focused on delineating the relationships between KRAS mutation subtypes and factors like immunotherapy markers and immune cell composition, in addition to examining survival rates, drug sensitivity, and PD-L1 responses corresponding to distinct KRAS subtypes.We found that the G12V and G12D subtypes demonstrated elevated expressions of immunotherapy markers, implying a potentially enhanced benefit from immunotherapy. Significant variations were identified in the distribution of naive B cells, activated CD4+ memory T cells, and regulatory T cells (Tregs) across different KRAS mutant subtypes. A notable difference was observed in the Tumor Mutation Burden (TMB) levels across the four KRAS subtypes, with the G12D subtype displaying the lowest TMB level. Furthermore, G12C subtype showcased the worst prognosis in terms of progression-free intervals (PFI), in stark contrast to the more favorable outcomes associated with the G12A subtype.Our study reveals that KRAS mutations exhibit considerable variability in predicting outcomes for LUAD patients undergoing ICI treatment. Thus, the evaluation of KRAS as a biomarker for ICIs necessitates recognizing the potential diversity inherent in KRAS mutations.Copyright © 2023 Wang, Tang, Li, Li and Su.