Department of Pediatrics, Division of Pediatric Hematology-Oncology, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093-0815, USA.
Moores Cancer Center, Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, CA, USA.
Pharmacol Ther. 2022 Jul;235:108114. doi: 10.1016/j.pharmthera.2022.108114. Epub 2022 Feb 2.
Myeloid-derived suppressor cells (MDSCs) are immune cells of the myeloid lineage that progressively accumulate in tumors and play an important role in promoting tumor growth. MDSCs interact with other immune cells present in the tumor microenvironment (TME) and utilize multiple mechanisms to promote immunosuppression. On the other hand, natural killer (NK) cells are cytotoxic cells of the innate immune system and work as one of the first lines of defense against tumors. However, the role of MDSCs in regulating or suppressing NK cells within the TME is poorly understood. This review discusses MDSC-associated immunosuppression, the mechanisms regulating communication between MDSCs and NK cells in the tumor microenvironment, and how MDSC may impact NK-cell-based immunotherapies. We also explore various strategies to increase NK cell cytotoxicity by blocking MDSC-mediated immunosuppression with the goal of enhancing cell based anti-cancer therapeutics.
髓系来源的抑制性细胞(MDSCs)是髓系细胞的免疫细胞,它们在肿瘤中逐渐积累,在促进肿瘤生长中发挥重要作用。MDSCs 与肿瘤微环境(TME)中存在的其他免疫细胞相互作用,并利用多种机制促进免疫抑制。另一方面,自然杀伤(NK)细胞是先天免疫系统的细胞毒性细胞,是抵抗肿瘤的第一道防线之一。然而,MDSC 在调节或抑制 TME 中的 NK 细胞方面的作用还知之甚少。这篇综述讨论了 MDSC 相关的免疫抑制、调节肿瘤微环境中 MDSC 和 NK 细胞之间通讯的机制,以及 MDSC 如何影响基于 NK 细胞的免疫疗法。我们还探讨了通过阻断 MDSC 介导的免疫抑制来增加 NK 细胞细胞毒性的各种策略,以增强基于细胞的抗癌治疗。