Cancer Research Center, Qatar Biomedical Research Institute, College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
Institute of Cancer Sciences, University of Manchester, Manchester, UK.
Immunol Cell Biol. 2018 Oct;96(9):888-897. doi: 10.1111/imcb.12054. Epub 2018 Apr 22.
Immune evasion is a characteristic of most human malignancies and is induced via various mechanisms. Immunosuppressive cells, including myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), are key mediators in assisting tumors to escape immune surveillance. Expansion of MDSC, Treg and elevated levels of immune checkpoints (IC) are frequently detected in the tumor microenvironment and periphery of cancer patients. Various therapeutic agents have been shown to target MDSC and to block IC for inducing anti-tumor immunity and reversal of tumor immune escape. Importantly, some recent studies have shown that MDSC targeting improves the efficacy of IC blockade in cancer therapy. However, there is a pressing need to improve our understanding of the distinct role of these cells to develop combination therapy that attacks tumor cells from all frontiers to improve cancer therapeutics. Herein, we discuss the role of MDSC in cancer progression, interactions with IC in the context of anti-cancer immunity and the current therapeutic strategies to target MDSC and block IC in cancer.
免疫逃避是大多数人类恶性肿瘤的特征,可通过多种机制诱导。免疫抑制细胞,包括髓系来源的抑制细胞(MDSC)和调节性 T 细胞(Treg),是协助肿瘤逃避免疫监视的关键介质。在肿瘤微环境和癌症患者的外周血中,经常检测到 MDSC、Treg 的扩增和免疫检查点(IC)水平的升高。已经有多种治疗药物被证明可以靶向 MDSC 并阻断 IC,以诱导抗肿瘤免疫和逆转肿瘤免疫逃逸。重要的是,一些最近的研究表明,针对 MDSC 的治疗可以提高 IC 阻断在癌症治疗中的疗效。然而,迫切需要提高我们对这些细胞的不同作用的理解,以开发联合治疗方法,从各个前沿攻击肿瘤细胞,从而改善癌症治疗效果。在此,我们讨论了 MDSC 在癌症进展中的作用、在抗肿瘤免疫背景下与 IC 的相互作用,以及目前靶向 MDSC 和阻断 IC 治疗癌症的治疗策略。