Pyzer Athalia Rachel, Cole Leandra, Rosenblatt Jacalyn, Avigan David E
Bone Marrow Transplant, Beth Israel Deaconess Medical Center, Center for Life Sciences, CLS724, Boston, MA.
Int J Cancer. 2016 Nov 1;139(9):1915-26. doi: 10.1002/ijc.30232. Epub 2016 Jul 12.
The tumor microenvironment consists of an immunosuppressive niche created by the complex interactions between cancer cells and surrounding stromal cells. A critical component of this environment are myeloid-derived suppressor cells (MDSCs), a heterogeneous group of immature myeloid cells arrested at different stages of differentiation and expanded in response to a variety of tumor factors. MDSCs exert diverse effects in modulating the interactions between immune effector cells and the malignant cells. An increased presence of MDSCs is associated with tumor progression, poorer outcomes, and decreased effectiveness of immunotherapeutic strategies. In this article, we will review our current understanding of the mechanisms that underlie MDSC expansion and their immune-suppressive function. Finally, we review the preclinical studies and clinical trials that have attempted to target MDSCs, in order to improve responses to cancer therapies.
肿瘤微环境由癌细胞与周围基质细胞之间复杂相互作用所形成的免疫抑制微环境组成。该环境的一个关键组成部分是髓系来源的抑制性细胞(MDSCs),这是一组异质性的未成熟髓系细胞,它们在不同分化阶段停滞,并因多种肿瘤因子而扩增。MDSCs在调节免疫效应细胞与恶性细胞之间的相互作用方面发挥着多种作用。MDSCs数量的增加与肿瘤进展、较差的预后以及免疫治疗策略有效性的降低有关。在本文中,我们将综述目前对MDSC扩增及其免疫抑制功能背后机制的理解。最后,我们回顾了旨在靶向MDSCs以改善癌症治疗反应的临床前研究和临床试验。