肿瘤细胞治疗研究
英文原题：Targeting KRAS in colorectal cancer immunotherapy: rationale, challenges and future directions.
Kirsten大鼠肉瘤（KRAS）在结直肠癌（CRC）中经常发生突变。
Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）在结直肠癌（CRC）中频繁突变。近年来，突变KRAS已摆脱“不可成药”的标签，目前已有两种临床获批的抑制剂可用。除了异常激活肿瘤细胞内在生长信号外，致癌KRAS还促进免疫抑制性肿瘤微环境（TME）的形成，尤其是在CRC中。这表明KRAS抑制可能增强对免疫治疗的应答，支持将突变KRAS抑制剂与免疫检查点阻断（ICB）联合使用的合理性。突变KRAS被认为是一个理想的免疫学靶点。新兴的治疗方法，包括疫苗、TCR-T细胞疗法和抗体，正在被开发用于治疗KRAS突变CRC患者，这些方法利用突变KRAS产生的肽或肽/主要组织相容性复合体I类（MHC-I）复合物。在此，我们概述了CRC免疫治疗中靶向突变KRAS的策略，并讨论了挑战和未来方向。
Kirsten rat sarcoma (KRAS) is frequently mutated in colorectal cancer (CRC). In recent years, mutant KRAS has shed its "undruggable" label, with two clinically approved inhibitors now available. Besides aberrantly activating intrinsic tumor cell growth signaling, oncogenic KRAS contributes to the development of an immunosuppressive tumor microenvironment (TME), especially in CRC. This suggests KRAS inhibition may enhance responsiveness to immunotherapy, supporting the rationale for combining mutant KRAS inhibitors with immune checkpoint blockade (ICB). Mutant KRAS is considered as an ideal immunological target. Emerging therapeutics, including vaccines, TCR-T cell therapies and antibodies, are being developed to treat KRAS-mutant CRC patients that leverage peptides or peptide/major histocompatibility complex class I (MHC-I) complexes generated by mutant KRAS. Here, we provide an overview of targeting mutant KRAS in CRC immunotherapy, discussing challenges and future directions.
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