克拉斯
主要组织相容性复合体
胰腺癌
免疫系统
生物
癌症研究
癌症
肿瘤微环境
突变体
免疫学
突变
基因
遗传学
作者
Noah Cheng,Robert H. Vonderheide
标识
DOI:10.1016/j.trecan.2023.07.004
摘要
The 40-year desire to target the mutant Kirsten rat sarcoma (KRAS) gene (mKRAS) therapeutically is being realized with more and more broadly applicable and tumor-specific small-molecule inhibitors. Immunologically, mKRAS has equal desirability as a target. Tumor KRAS signaling plays a large role in shaping the immunosuppressive nature of the tumor microenvironment, especially in pancreatic cancer, leaving mKRAS inhibitors with potentially powerful immune modulatory capabilities that could be exploited in immunological–oncological combinations. mKRAS is itself an immunological antigen, a ‘shared neoepitope’ linked to the oncogenic process, validated biochemically and immunologically. Novel approaches in the clinic are taking advantage of the fact that mKRAS peptides are naturally processed and presented in tumors by the major histocompatibility complex (MHC).
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