Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States.
Front Immunol. 2021 May 5;12:633205. doi: 10.3389/fimmu.2021.633205. eCollection 2021.
The tumor microenvironment (TME) is a complex and heterogeneous environment composed of cancer cells, tumor stroma, a mixture of tissue-resident and infiltrating immune cells, secreted factors, and extracellular matrix proteins. Natural killer (NK) cells play a vital role in fighting tumors, but chronic stimulation and immunosuppression in the TME lead to NK cell exhaustion and limited antitumor functions. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive activity that gradually accumulate in tumor tissues. MDSCs interact with innate and adaptive immune cells and play a crucial role in negatively regulating the immune response to tumors. This review discusses MDSC-mediated NK cell regulation within the TME, focusing on critical cellular and molecular interactions. We review current strategies that target MDSC-mediated immunosuppression to enhance NK cell cytotoxic antitumor activity. We also speculate on how NK cell-based antitumor immunotherapy could be improved.
肿瘤微环境（TME）是一个复杂且异质的环境，由癌细胞、肿瘤基质、组织驻留和浸润免疫细胞的混合物、分泌因子和细胞外基质蛋白组成。自然杀伤（NK）细胞在抗肿瘤中发挥着重要作用，但 TME 中的慢性刺激和免疫抑制导致 NK 细胞耗竭和有限的抗肿瘤功能。髓系来源的抑制细胞（MDSC）是一群具有强大免疫抑制活性的异质性髓系细胞，它们逐渐在肿瘤组织中积累。MDSC 与先天和适应性免疫细胞相互作用，在负性调节对肿瘤的免疫反应中发挥关键作用。这篇综述讨论了 MDSC 在 TME 中对 NK 细胞的调节，重点介绍了关键的细胞和分子相互作用。我们回顾了目前靶向 MDSC 介导的免疫抑制以增强 NK 细胞细胞毒性抗肿瘤活性的策略。我们还推测了如何改善基于 NK 细胞的抗肿瘤免疫疗法。
