自然杀伤 (NK) 细胞在抗肿瘤和抗病毒反应中发挥着至关重要的作用。然而，癌细胞可以通过分泌细胞因子或其他因子来改变自身或微环境，阻碍 NK 细胞激活并促进细胞毒性较小的表型。这些耐药机制通常被称为“癌症标志”，受到癌基因激活的显着影响，影响了大多数（如果不是全部）所描述的标志。与癌基因和其他类型的基因一样，肿瘤抑制基因在癌症过程中经常发生突变或修饰。传统上，这些基因与失控的肿瘤生长和细胞凋亡抵抗有关。最近的证据表明致癌突变不仅限于调节细胞死亡/增殖程序，还影响癌症免疫监视。虽然对 T 细胞进行了更多研究，但获得的结果强调 NK 细胞是通过调节致癌活性来增强肿瘤细胞消除的新兴关键主角。最近的一些研究强调了致癌突变在 NK 细胞介导的癌症识别中的关键作用，影响肿瘤微环境中的血管生成、应激配体和信号平衡。这篇综述将批判性地审视最近的发现，将致癌突变与 NK 细胞介导的癌症免疫监视相关联，这是一个相对未被充分探索的领域，特别是在免疫检查点抑制剂和 CAR-T 细胞主导的时代。基于这些见解，我们将探索改进基于 NK 细胞的免疫疗法的机会，这种疗法越来越被认为是治疗低抗原肿瘤的有前途的替代方案，在安全性和制造适用性方面具有显着优势。© 2024 作者。经泰勒许可出版

Natural killer (NK) cells play a crucial role in antitumoral and antiviral responses. Yet, cancer cells can alter themselves or the microenvironment through the secretion of cytokines or other factors, hindering NK cell activation and promoting a less cytotoxic phenotype. These resistance mechanisms, often referred to as the "hallmarks of cancer" are significantly influenced by the activation of oncogenes, impacting most, if not all, of the described hallmarks. Along with oncogenes, other types of genes, the tumor suppressor genes are frequently mutated or modified during cancer. Traditionally, these genes have been associated with uncontrollable tumor growth and apoptosis resistance. Recent evidence suggests oncogenic mutations extend beyond modulating cell death/proliferation programs, influencing cancer immunosurveillance. While T cells have been more studied, the results obtained highlight NK cells as emerging key protagonists for enhancing tumor cell elimination by modulating oncogenic activity. A few recent studies highlight the crucial role of oncogenic mutations in NK cell-mediated cancer recognition, impacting angiogenesis, stress ligands, and signaling balance within the tumor microenvironment. This review will critically examine recent discoveries correlating oncogenic mutations to NK cell-mediated cancer immunosurveillance, a relatively underexplored area, particularly in the era dominated by immune checkpoint inhibitors and CAR-T cells. Building on these insights, we will explore opportunities to improve NK cell-based immunotherapies, which are increasingly recognized as promising alternatives for treating low-antigenic tumors, offering significant advantages in terms of safety and manufacturing suitability.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.