Kumagai Shogo, Momoi Yusaku, Nishikawa Hiroyoshi
Division of Cancer Immunology, Research Institute, National Cancer Center, Tokyo 104-0045, Japan.
Division of Cancer Immunology, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Chiba 277-8577, Japan.
Sci Immunol. 2025 Mar 28;10(105):eabo5570. doi: 10.1126/sciimmunol.abo5570.
The process of tumor development involves tumor cells eluding detection and suppression of immune responses, which can cause decreased tumor cell antigenicity, expression of immunosuppressive molecules, and immunosuppressive cell recruitment to the tumor microenvironment (TME). Immunologically and genomically integrated analysis (immunogenomic analysis) of patient specimens has revealed that oncogenic aberrant signaling is involved in both carcinogenesis and immune evasion. In noninflamed cancers such as ()-mutated lung cancers, genetic abnormalities in cancer cells contribute to the formation of an immunosuppressive TME by recruiting immunosuppressive cells, which cannot be fully explained by the cancer immunoediting hypothesis. This review summarizes the latest findings regarding the links between cancer genetic abnormalities and immunosuppression causing clinical resistance to immunotherapy. We propose the concepts of immunogenomic cancer evolution, in which cancer cell genomic evolution shapes the immunosuppressive TME, and immunogenomic precision medicine, in which cancer immunotherapy can be combined with molecularly targeted reagents that modulate the immunosuppressive TME.
肿瘤发展过程涉及肿瘤细胞逃避免疫反应的检测和抑制，这会导致肿瘤细胞抗原性降低、免疫抑制分子表达以及免疫抑制细胞被招募至肿瘤微环境（TME）。对患者标本进行免疫和基因组综合分析（免疫基因组分析）发现，致癌异常信号传导参与了肿瘤发生和免疫逃逸过程。在诸如（）突变型肺癌等非炎症性癌症中，癌细胞的基因异常通过招募免疫抑制细胞促成免疫抑制性TME的形成，而癌症免疫编辑假说无法完全解释这一现象。本综述总结了有关癌症基因异常与导致免疫治疗临床耐药的免疫抑制之间联系的最新研究结果。我们提出了免疫基因组癌症进化的概念，即癌细胞基因组进化塑造免疫抑制性TME；以及免疫基因组精准医学的概念，即癌症免疫治疗可与调节免疫抑制性TME的分子靶向试剂相结合。
