Toll-like receptors (TLR)s are homo- or heterodimeric proteins, whose structure and function were widely described in the antigen presenting cells (APC), such as Dendritic cells (DC). Recently, the expression and the role of TLRs in fighting against pathogens, was described also in NK cells. Their activation and functional properties can be directly and indirectly modulated by agonists for TLRs. In particular CD56^bright NK cells subset, that is the most abundant NK cell subset in tissues and tumor microenvironment (TME), was mostly activated in terms of pro-inflammatory cytokine production, proliferation and cytotoxicity, by agonists specific for endosomal TLR8. The interplay between DC and NK, that depends on both cell-to-cell contact and soluble factors such as cytokines, promote both DC maturation and NK cell activation. Based on this concept, a TLR based immunotherapy aimed to activate NK-DC axis, may modulate TME by inducing a pro-inflammatory phenotype, thus improving DC ability to present tumor-associated antigens to T cells, and NK cell cytotoxicity against tumor cells. In this mini-review, we report data of recent literature about TLRs on human NK cells and their application as adjuvant in cancer vaccines or in combined tumor immunotherapy.

Toll 样受体 (TLR) 是同二聚体或异二聚体蛋白，其结构和功能在抗原呈递细胞 (APC)（例如树突状细胞 (DC)）中被广泛描述。最近，TLR 在对抗病原体中的表达和作用也在 NK 细胞中得到描述。TLR 激动剂可以直接或间接调节它们的激活和功能特性。特别是 CD56bright ^NK细胞亚群，即组织和肿瘤微环境 (TME) 中最丰富的 NK 细胞亚群，主要通过内体 TLR8 特异性激动剂激活促炎细胞因子的产生、增殖和细胞毒性。DC 和 NK 之间的相互作用取决于细胞间接触和细胞因子等可溶性因子，促进 DC 成熟和 NK 细胞激活。基于这一概念，基于TLR的免疫疗法旨在激活NK-DC轴，可以通过诱导促炎表型来调节TME，从而提高DC向T细胞呈递肿瘤相关抗原的能力，以及NK细胞针对肿瘤细胞的细胞毒性。在这篇小综述中，我们报告了有关人类 NK 细胞 TLR 及其在癌症疫苗或联合肿瘤免疫治疗中作为佐剂的应用的最新文献数据。