Radiotherapy and OncoImmunology Laboratory, Department of Radiation Oncology, Radboud University Medical Center, Geert Grooteplein Zuid 32, 6525 GA Nijmegen, The Netherlands.
Radiotherapy and OncoImmunology Laboratory, Department of Radiation Oncology, Radboud University Medical Center, Geert Grooteplein Zuid 32, 6525 GA Nijmegen, The Netherlands.
Cell Immunol. 2021 Apr;362:104298. doi: 10.1016/j.cellimm.2021.104298. Epub 2021 Jan 30.
Myeloid derived suppressor cells (MDSCs) are a highly heterogeneous population of immature immune cells with immunosuppressive functions that are recruited to the tumor microenvironment (TME). MDSCs promote tumor growth and progression by inhibiting immune effector cell proliferation and function. MDSCs are affected by both novel anti-cancer therapies targeting the immune system to promote anti-tumor immunity, as well as by conventional treatments such as radiotherapy. Following radiotherapy, cytoplasmic double stranded DNA stimulates the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway, resulting in type I interferon production. Effectiveness of radiotherapy and cGAS/STING signaling are closely intertwined: activation of cGAS and STING is key to generate systemic anti-tumor immunity after irradiation. This review focuses on how radiotherapy and cGAS/STING signaling in MDSCs and/or tumor cells impact MDSC recruitment, expansion and function. The influence of conventional and ablative radiotherapy treatment schedules, inflammatory response following radiotherapy, and hypoxia are discussed as MDSC modulators.
髓系来源的抑制性细胞（MDSCs）是一群具有免疫抑制功能的未成熟免疫细胞，它们被招募到肿瘤微环境（TME）中。MDSCs 通过抑制免疫效应细胞的增殖和功能来促进肿瘤的生长和进展。MDSCs 受到新型抗癌疗法的影响，这些疗法靶向免疫系统以促进抗肿瘤免疫，也受到常规治疗如放疗的影响。放疗后，细胞质双链 DNA 刺激环鸟苷酸-腺苷酸合酶（cGAS）/干扰素基因刺激物（STING）途径，导致 I 型干扰素的产生。放疗和 cGAS/STING 信号的有效性密切相关：cGAS 和 STING 的激活是照射后产生全身抗肿瘤免疫的关键。这篇综述重点介绍了放疗和 MDSCs 和/或肿瘤细胞中的 cGAS/STING 信号如何影响 MDSC 的募集、扩增和功能。讨论了常规和消融放疗方案、放疗后的炎症反应和缺氧作为 MDSC 调节剂的影响。
