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针对肿瘤微环境中的髓系细胞。

Targeting myeloid cells in the tumor sustaining microenvironment.

机构信息

Department of Dermatology, University Medical Center, Mainz, Germany.

Department of Dermatology, University Medical Center, Mainz, Germany; German Cancer Consortium (DKTK), partner site Mainz, and German Cancer Research Center (DKFZ), Heidelberg, Germany.

出版信息

Cell Immunol. 2019 Sep;343:103713. doi: 10.1016/j.cellimm.2017.10.013. Epub 2017 Nov 2.

Abstract

Myeloid cells are the most abundant cells in the tumor microenvironment (TME). The tumor recruits and modulates endogenous myeloid cells to tumor-associated macrophages (TAM), dendritic cells (DC), myeloid-derived suppressor cells (MDSC) and neutrophils (TAN), to sustain an immunosuppressive environment. Pathologically overexpressed mediators produced by cancer cells like granulocyte-macrophage colony-stimulating- and vascular endothelial growth factor induce myelopoiesis in the bone marrow. Excess of myeloid cells in the blood, periphery and tumor has been associated with tumor burden. In cancer, myeloid cells are kept at an immature state of differentiation to be diverted to an immunosuppressive phenotype. Here, we review human myeloid cells in the TME and the mechanisms for sustaining the hallmarks of cancer. Simultaneously, we provide an introduction into current and novel therapeutic approaches to redirect myeloid cells from a cancer promoting to a rather inflammatory, cancer inhibiting phenotype. In addition, the role of platelets for tumor promotion is discussed.

摘要

髓系细胞是肿瘤微环境 (TME) 中最丰富的细胞。肿瘤招募并调节内源性髓系细胞,使其成为肿瘤相关巨噬细胞 (TAM)、树突状细胞 (DC)、髓系来源的抑制细胞 (MDSC) 和中性粒细胞 (TAN),以维持免疫抑制环境。癌细胞病理性过表达的介质,如粒细胞-巨噬细胞集落刺激因子和血管内皮生长因子,诱导骨髓中的髓系细胞生成。血液、外周和肿瘤中过多的髓系细胞与肿瘤负担有关。在癌症中,髓系细胞保持在未成熟的分化状态,以转向免疫抑制表型。在这里,我们综述了 TME 中的人类髓系细胞及其维持癌症特征的机制。同时,我们介绍了目前和新型的治疗方法,以将髓系细胞从促进癌症的表型重新定向为炎症、抑制癌症的表型。此外,还讨论了血小板在肿瘤促进中的作用。

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