Trikha Prashant, Carson William E
Comprehensive Cancer Center, The Ohio State University, USA.
Comprehensive Cancer Center, The Ohio State University, USA; Department of Surgery, The Ohio State University, Columbus, OH 43210, USA.
Biochim Biophys Acta. 2014 Aug;1846(1):55-65. doi: 10.1016/j.bbcan.2014.04.003. Epub 2014 Apr 13.
The immune system has evolved mechanisms to protect the host from the deleterious effects of inflammation. The generation of immune suppressive cells like myeloid derived suppressor cells (MDSCs) that can counteract T cell responses represents one such strategy. There is an accumulation of immature myeloid cells or MDSCs in bone marrow (BM) and lymphoid organs under pathological conditions such as cancer. MDSCs represent a population of heterogeneous myeloid cells comprising of macrophages, granulocytes and dendritic cells that are at early stages of development. Although, the precise signaling pathways and molecular mechanisms that lead to MDSC generation and expansion in cancer remains to be elucidated. It is widely believed that perturbation of signaling pathways involved during normal hematopoietic and myeloid development under pathological conditions such as tumorogenesis contributes to the development of suppressive myeloid cells. In this review we discuss the role played by key signaling pathways such as PI3K, Ras, Jak/Stat and TGFb during myeloid development and how their deregulation under pathological conditions can lead to the generation of suppressive myeloid cells or MDSCs. Targeting these pathways should help in elucidating mechanisms that lead to the expansion of MDSCs in cancer and point to methods for eliminating these cells from the tumor microenvironment.
免疫系统已经进化出保护宿主免受炎症有害影响的机制。产生能够抵消T细胞反应的免疫抑制细胞，如髓系来源的抑制细胞（MDSCs），就是这样一种策略。在癌症等病理条件下，骨髓（BM）和淋巴器官中会积累未成熟的髓系细胞或MDSCs。MDSCs代表一群异质性的髓系细胞，包括处于发育早期的巨噬细胞、粒细胞和树突状细胞。尽管导致癌症中MDSC产生和扩增的确切信号通路和分子机制仍有待阐明。人们普遍认为，在肿瘤发生等病理条件下，正常造血和髓系发育过程中涉及的信号通路受到干扰会导致抑制性髓系细胞的产生。在这篇综述中，我们讨论了PI3K、Ras、Jak/Stat和TGFb等关键信号通路在髓系发育过程中所起的作用，以及它们在病理条件下的失调如何导致抑制性髓系细胞或MDSCs的产生。针对这些通路应该有助于阐明导致癌症中MDSCs扩增的机制，并指出从肿瘤微环境中消除这些细胞的方法。
