Over recent years, the use of immune checkpoint inhibitors (ICI) has progressed to first and second-line treatments in several cancer types, transforming patient outcomes. While these treatments target T cell checkpoints, such as PD-1, LAG3 and CTLA-4, their efficacy can be compromised through adaptive resistance whereby tumors acquire mutations in genes regulating neoantigen presentation by MHC-I [93]. ICI-responsive tumor types such as advanced metastatic melanoma typically have a high mutational burden and immune infiltration; however, most patients still do not benefit from ICI monotherapy for a number of reasons [94]. This highlights the need for novel immunotherapy strategies that evoke the immune control of tumor cells with low neoantigen/MHC-I expression, overcome immune suppressive tumor microenvironments and promote tumor inflammation. In this regard, targeting natural killer (NK) cells may offer a solution to some of these bottlenecks.

近年来，免疫检查点抑制剂（ICI）的使用已发展为多种癌症类型的一线和二线治疗，改变了患者的治疗结果。虽然这些治疗针对 T 细胞检查点，如 PD-1、LAG3 和 CTLA-4，但它们的疗效可能会因适应性耐药而受到损害，适应性耐药使肿瘤在调节MHC-I 呈递新抗原的[93]。ICI 反应性肿瘤类型，例如晚期转移性黑色素瘤，通常具有高突变负荷和免疫浸润；然而，由于多种原因，大多数患者仍然没有从 ICI 单一疗法中受益[94]。这凸显了对新型免疫治疗策略的需求，该策略能够唤起对低新抗原/MHC-I表达的肿瘤细胞的免疫控制，克服免疫抑制性肿瘤微环境并促进肿瘤炎症。在这方面，靶向自然杀伤（NK）细胞可能为其中一些瓶颈提供解决方案。