Department of Molecular Medicine, Laboratory Affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Front Immunol. 2021 Dec 17;12:787116. doi: 10.3389/fimmu.2021.787116. eCollection 2021.
NK cells are innate lymphoid cells endowed with cytotoxic capacity that play key roles in the immune surveillance of tumors. Increasing evidence indicates that NK cell anti-tumor response is shaped by bidirectional interactions with myeloid cell subsets such as dendritic cells (DCs) and macrophages. DC-NK cell crosstalk in the tumor microenvironment (TME) strongly impacts on the overall NK cell anti-tumor response as DCs can affect NK cell survival and optimal activation while, in turn, NK cells can stimulate DCs survival, maturation and tumor infiltration through the release of soluble factors. Similarly, macrophages can either shape NK cell differentiation and function by expressing activating receptor ligands and/or cytokines, or they can contribute to the establishment of an immune-suppressive microenvironment through the expression and secretion of molecules that ultimately lead to NK cell inhibition. Consequently, the exploitation of NK cell interaction with DCs or macrophages in the tumor context may result in an improvement of efficacy of immunotherapeutic approaches.
自然杀伤 (NK) 细胞是具有细胞毒性的先天淋巴细胞，在肿瘤的免疫监视中发挥着关键作用。越来越多的证据表明，NK 细胞的抗肿瘤反应受到与髓样细胞亚群（如树突状细胞 (DC) 和巨噬细胞）之间的双向相互作用的影响。肿瘤微环境 (TME) 中的 DC-NK 细胞串扰强烈影响整体 NK 细胞抗肿瘤反应，因为 DC 可以影响 NK 细胞的存活和最佳激活，而反过来，NK 细胞可以通过释放可溶性因子刺激 DC 的存活、成熟和肿瘤浸润。同样，巨噬细胞可以通过表达激活受体配体和/或细胞因子来塑造 NK 细胞的分化和功能，或者通过表达和分泌最终导致 NK 细胞抑制的分子来促进免疫抑制微环境的建立。因此，利用 NK 细胞与 DC 或巨噬细胞在肿瘤环境中的相互作用可能会提高免疫治疗方法的疗效。
