Department of Immunology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
J Cell Physiol. 2019 Jul;234(7):9966-9981. doi: 10.1002/jcp.27923. Epub 2018 Dec 7.
The immunosuppressive features of tumor lesions participate not only as one of the major players inducing cancer progression but also a big challenge for effective immunotherapy. It has been found that immunosuppression associated with chronic inflammatory factors, such as growth factors, cytokines, and chemokines is generated by stroma and tumor cells. Chronic and exhaustive secretion of these mediators triggers the generation of myeloid-derived suppressor cells (MDSCs) demonstrating one of the key players engaged in tumor immunosuppression. In point of fact, direct cell-to-cell contact is a prerequisite for immunosuppressive functions of MDSCs. From the clinical perspective, the frequency of peripheral blood MDSCs is correlated with clinical stage and therapeutic response in various cancers. Furthermore, MDSCs are involved in chemoresistant settings. Altogether, it is a rational therapeutic approach to block the fierce cycle in which MDSCs are developed and infiltrated to favor cancer progression. In this review, we will summarize recent findings of MDSCs in tumor progression and discuss potential therapeutic strategies that could be evaluated in future clinical trials.
肿瘤病变的免疫抑制特征不仅是诱导癌症进展的主要因素之一,也是有效免疫治疗的一大挑战。已经发现,与慢性炎症因子(如生长因子、细胞因子和趋化因子)相关的免疫抑制是由基质细胞和肿瘤细胞产生的。这些介质的慢性和过度分泌会触发髓源抑制细胞(MDSCs)的产生,表明其是参与肿瘤免疫抑制的关键因素之一。事实上,细胞间的直接接触是 MDSCs 免疫抑制功能的前提。从临床角度来看,外周血 MDSCs 的频率与各种癌症的临床分期和治疗反应相关。此外,MDSCs 还参与了化疗耐药的情况。总之,阻断 MDSCs 的发展和浸润有利于癌症进展的激烈循环是一种合理的治疗方法。在这篇综述中,我们将总结 MDSCs 在肿瘤进展中的最新发现,并讨论未来临床试验中可能评估的潜在治疗策略。