Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany.
J Clin Invest. 2023 Jul 3;133(13):e170762. doi: 10.1172/JCI170762.
Despite the remarkable success of immune checkpoint inhibitors (ICIs) in melanoma treatment, resistance to them remains a substantial clinical challenge. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid cells that can suppress antitumor immune responses mediated by T and natural killer cells and promote tumor growth. They are major contributors to ICI resistance and play a crucial role in creating an immunosuppressive tumor microenvironment. Therefore, targeting MDSCs is considered a promising strategy to improve the therapeutic efficacy of ICIs. This Review describes the mechanism of MDSC-mediated immune suppression, preclinical and clinical studies on MDSC targeting, and potential strategies for inhibiting MDSC functions to improve melanoma immunotherapy.
尽管免疫检查点抑制剂 (ICIs) 在黑色素瘤治疗中取得了显著的成功，但对它们的耐药性仍然是一个重大的临床挑战。髓系来源的抑制细胞 (MDSCs) 是一种异质性的髓系细胞群体，能够抑制 T 细胞和自然杀伤细胞介导的抗肿瘤免疫反应，并促进肿瘤生长。它们是 ICI 耐药的主要贡献者，并在创建免疫抑制性肿瘤微环境中发挥关键作用。因此，靶向 MDSCs 被认为是提高 ICI 治疗效果的一种有前途的策略。本综述描述了 MDSC 介导的免疫抑制的机制、针对 MDSC 的临床前和临床研究，以及抑制 MDSC 功能以改善黑色素瘤免疫治疗的潜在策略。
