在过去十年中，免疫疗法领域取得了巨大的进展，其通过激活免疫系统来对抗肿瘤。与此同时，在发现抑制癌症生长的致癌驱动基因的药物方面也取得了重大进展。然而，将免疫疗法与针对致癌驱动通路的药物相结合方面进展甚微。人类癌症中的一些重要致癌基因编码RAS家族蛋白；尽管人们一直难以针对这些蛋白进行治疗，但最近研制出了一些能抑制一种特定突变形式的KRAS (G12C) 的药物。这些药物改善了携带这种突变的肺癌患者的治疗效果，但在初始反应后出现的获得性药物耐药性限制了它们在整体生存率上的影响。由于致癌KRAS所控制的信号网络具有免疫抑制性质，针对KRAS G12C的靶向抑制可以间接影响抗肿瘤免疫，而且不会对免疫细胞中正常RAS蛋白的关键作用产生影响。这为联合使用免疫检查点阻断提供了理论基础，在某些临床前癌症模型中可能会带来额外的联合治疗效益。然而，临床试验中，KRAS G12C抑制剂与PD-(L)1阻断联合治疗尚未显示出改善的治疗结果，部分原因是由于治疗毒性。对致癌KRAS如何推动免疫逃逸以及突变特异性KRAS抑制如何影响肿瘤微环境的更深入了解，可以为将RAS抑制与免疫疗法相结合提供新的方法。

While the past decade has seen great strides in the development of immunotherapies that reactivate the immune system against tumors, there have also been major advances in the discovery of drugs blocking oncogenic drivers of cancer growth. However, there has been very little progress in combining immunotherapies with drugs that target oncogenic driver pathways. Some of the most important oncogenes in human cancer encode RAS family proteins; although these have proven challenging to target, recently drugs have been approved that inhibit a specific mutant form of KRAS, G12C. These have improved the treatment of lung cancer patients harboring this mutation but development of acquired drug resistance after initial responses has limited the impact on overall survival. Due to the immunosuppressive nature of the signaling network controlled by oncogenic KRAS, targeted KRAS G12C inhibition can indirectly affect anti-tumor immunity, and does so without compromising the critical role of normal RAS proteins in immune cells. This serves as a rationale for combination with immune checkpoint blockade, which can provide additional combinatorial therapeutic benefit in some pre-clinical cancer models. However, in clinical trials, combination of KRAS G12C inhibitors with PD-(L)1 blockade has yet to show improved outcome, in part due to treatment toxicities. A greater understanding of how oncogenic KRAS drives immune evasion and how mutant specific KRAS inhibition impacts the tumor microenvironment can lead to novel approaches to combining RAS inhibition with immunotherapies.