Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, MG, Brazil.
Tumor Biomarkers and Osteoimmunology Laboratory, Av. Pará - 1720 - Block 6T, Room 07 - District Umuarama, Uberlândia, MG, Brazil.
J Cancer Res Clin Oncol. 2023 Aug;149(9):6661-6673. doi: 10.1007/s00432-023-04575-8. Epub 2023 Jan 12.
Natural killer cells are critical players in the antitumor immune response due to their ability to destroy target cells through cytotoxic activity and other means. However, this response is inhibited in the tumor microenvironment, where a crippling hypoxic environment and several inhibitory molecules bind to NK cells to trigger an anergic state. Inhibitory receptors such as PD-1, NK2GA, KIR, TIGIT, and LAG-3 have been associated with inhibition of NK cells in multiple cancer types. Binding to these receptors leads to loss of cytotoxicity, lower proliferation and metabolic rates, and even apoptosis. While these receptors are important for avoiding auto-immunity, in a pathological setting like malignant neoplasms they are disadvantageous for the individual's immune system to combat cancer cells. The use of monoclonal antibodies to block these receptors contributes to cancer therapy by preventing the inhibition of NK cells. In this review, the impact of NK cell inhibition and activation on cancer therapy was summarized and an overview of the blockade of inhibitory pathways by monoclonal antibodies was provided.
自然杀伤细胞 (NK 细胞) 通过细胞毒性活性和其他方式破坏靶细胞，是抗肿瘤免疫反应的关键参与者。然而，这种反应在肿瘤微环境中受到抑制，在肿瘤微环境中，破坏性的缺氧环境和几种抑制性分子与 NK 细胞结合，引发无能状态。PD-1、NK2GA、KIR、TIGIT 和 LAG-3 等抑制性受体与多种癌症类型中 NK 细胞的抑制有关。与这些受体结合会导致细胞毒性丧失、增殖和代谢率降低，甚至凋亡。虽然这些受体对于避免自身免疫很重要，但在恶性肿瘤等病理情况下，它们对个体的免疫系统对抗癌细胞是不利的。使用单克隆抗体阻断这些受体有助于癌症治疗，防止 NK 细胞被抑制。在这篇综述中，总结了 NK 细胞抑制和激活对癌症治疗的影响，并概述了单克隆抗体阻断抑制途径。
