Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Cell Immunol. 2021 May;363:104312. doi: 10.1016/j.cellimm.2021.104312. Epub 2021 Feb 12.
Myeloid-derived suppressor cells (MDSCs) impair protective anti-tumor immunity and remain major obstacles that stymie the effectiveness of promising cancer therapies. Diverse tumor-derived stressors galvanize the differentiation, intra-tumoral expansion, and immunomodulatory function of MDSCs. These tumor-associated 'axes of stress' underwrite the immunosuppressive programming of MDSCs in cancer and contribute to the phenotypic/functional heterogeneity that characterize tumor-MDSCs. This review discusses various tumor-associated axes of stress that direct MDSC development, accumulation, and immunosuppressive function, as well as current strategies aimed at overcoming the detrimental impact of MDSCs in cancer. To better understand the constellation of signals directing MDSC biology, we herein summarize the pivotal roles, signaling mediators, and effects of reactive oxygen/nitrogen species-related stress, chronic inflammatory stress, hypoxia-linked stress, endoplasmic reticulum stress, metabolic stress, and therapy-associated stress on MDSCs. Although therapeutic targeting of these processes remains mostly pre-clinical, intercepting signaling through the axes of stress could overcome MDSC-related immune suppression in tumor-bearing hosts.
髓系来源的抑制细胞（MDSCs）损害保护性抗肿瘤免疫，仍然是阻碍有前途的癌症治疗效果的主要障碍。各种肿瘤来源的应激源激发 MDSC 的分化、肿瘤内扩增和免疫调节功能。这些与肿瘤相关的“应激轴”为癌症中 MDSC 的免疫抑制编程提供了基础，并导致了肿瘤-MDSC 的表型/功能异质性。这篇综述讨论了各种与肿瘤相关的应激轴，这些应激轴直接指导 MDSC 的发育、积累和免疫抑制功能，以及目前旨在克服 MDSC 在癌症中不良影响的策略。为了更好地理解指导 MDSC 生物学的信号组合，我们在此总结了与活性氧/氮物种相关的应激、慢性炎症应激、缺氧相关应激、内质网应激、代谢应激和治疗相关应激相关的关键作用、信号介质和效应在 MDSCs 上。尽管这些过程的治疗靶向主要处于临床前阶段，但通过应激轴阻断信号可以克服肿瘤宿主中与 MDSC 相关的免疫抑制。
