Bottino Cristina, Picant Valentin, Vivier Eric, Castriconi Roberta
Department of Experimental Medicine (DIMES), University of Genova, Genoa, Italy.
Laboratory of Clinical and Experimental Immunology, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Immunol Rev. 2024 Nov;328(1):412-421. doi: 10.1111/imr.13384. Epub 2024 Aug 24.
Natural killer (NK) cells are innate immune effectors whose functions rely on receptors binding cytokines, recognizing self-molecules, or detecting danger signals expressed by virus-infected or tumor cells. The potent cytotoxic potential makes NK cells promising candidates for cancer immunotherapy. To enhance their activity strategies include cytokine administration, blocking of immune checkpoints, and designing of antibody-based NK cell engagers (NKCEs). NKCEs represent a cutting-edge approach to cancer therapy: they strengthen the NK-to-target cell interactions and optimize tumor killing, possibly overcoming the immunosuppressive tumor microenvironment. NK cells belong to the innate lymphoid cells (ILCs) and are categorized into different subsets also including cells with a memory-like phenotype: this complexity needs to be explored in the context of cancer immunotherapy, particularly when designing NKCEs. Two strategies to enhance NK cell activity in cancer patients can be adopted: activating patients' own NK cells versus the adoptive transfer of ex vivo activated NK cells. Furthermore, the capability of NKCEs to activate γδ T cells could have a significant synergistic effect in immunotherapy.
自然杀伤（NK）细胞是先天性免疫效应细胞，其功能依赖于与细胞因子结合的受体、识别自身分子或检测病毒感染或肿瘤细胞表达的危险信号。强大的细胞毒性潜力使NK细胞成为癌症免疫治疗的有希望的候选者。为了增强其活性，策略包括施用细胞因子、阻断免疫检查点以及设计基于抗体的NK细胞衔接器（NKCE）。NKCE是癌症治疗的前沿方法：它们加强了NK细胞与靶细胞的相互作用并优化肿瘤杀伤，可能克服免疫抑制性肿瘤微环境。NK细胞属于先天性淋巴细胞（ILC），并被分类为不同的亚群，其中还包括具有记忆样表型的细胞：这种复杂性需要在癌症免疫治疗的背景下进行探索，特别是在设计NKCE时。可以采用两种增强癌症患者NK细胞活性的策略：激活患者自身的NK细胞与过继转移体外激活的NK细胞。此外，NKCE激活γδT细胞的能力在免疫治疗中可能具有显著的协同效应。
