Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression.
Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression.
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DOI：
10.3389/fimmu.2018.00398
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发表时间：
2018
影响因子：
7.3
通讯作者：
Umansky V
中科院分区：
文献类型：
--
作者：
Fleming V;Hu X;Weber R;Nagibin V;Groth C;Altevogt P;Utikal J;Umansky V
免疫系统有许多复杂的机制来平衡广泛的免疫反应。独特的免疫抑制细胞可以保护过度的组织损伤和自身免疫性疾病。肿瘤细胞利用这些免疫抑制机制并建立强免疫抑制性肿瘤微环境（TME），其抑制抗肿瘤免疫应答，支持疾病进展。骨髓源性抑制细胞（MDSC）在这种免疫抑制性TME中起着至关重要的作用。这些细胞代表具有强免疫抑制潜力的不成熟髓样细胞的异质群体。它们抑制T细胞和NK细胞的抗肿瘤反应性。此外，它们促进血管生成，建立转移前小生境，并招募其他免疫抑制细胞，如调节性T细胞。越来越多的证据表明，MDSC的富集和激活与肿瘤的进展、复发和阴性临床结局相关。在过去的几年中，各种临床前研究和临床试验针对MDSC显示出可喜的成果。在这篇综述中，我们讨论了MDSC靶向的不同治疗方法，以克服免疫抑制性TME，提高当前肿瘤免疫治疗的效率。
The immune system has many sophisticated mechanisms to balance an extensive immune response. Distinct immunosuppressive cells could protect from excessive tissue damage and autoimmune disorders. Tumor cells take an advantage of those immunosuppressive mechanisms and establish a strongly immunosuppressive tumor microenvironment (TME), which inhibits antitumor immune responses, supporting the disease progression. Myeloid-derived suppressor cells (MDSC) play a crucial role in this immunosuppressive TME. Those cells represent a heterogeneous population of immature myeloid cells with a strong immunosuppressive potential. They inhibit an antitumor reactivity of T cells and NK cells. Furthermore, they promote angiogenesis, establish pre-metastatic niches, and recruit other immunosuppressive cells such as regulatory T cells. Accumulating evidences demonstrated that the enrichment and activation of MDSC correlated with tumor progression, recurrence, and negative clinical outcome. In the last few years, various preclinical studies and clinical trials targeting MDSC showed promising results. In this review, we discuss different therapeutic approaches on MDSC targeting to overcome immunosuppressive TME and enhance the efficiency of current tumor immunotherapies.