Human Tumor-Infiltrating Myeloid Cells: Phenotypic and Functional Diversity.
Human Tumor-Infiltrating Myeloid Cells: Phenotypic and Functional Diversity.
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DOI：
10.3389/fimmu.2017.00086
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发表时间：
2017
影响因子：
7.3
通讯作者：
Ryan EJ
中科院分区：
文献类型：
--
作者：
Elliott LA;Doherty GA;Sheahan K;Ryan EJ
我们目前对人类肿瘤驻留髓样细胞的理解在很大程度上基于小鼠模型的大量工作或使用免疫组织化学 (IHC) 计数患者肿瘤样本中的髓样细胞的研究。这导致了这样一个理论的建立：总的来说，肿瘤驻留的骨髓细胞要么是“原肿瘤”M2 巨噬细胞，要么是骨髓源性抑制细胞 (MDSC)。这一概念加速了我们对肿瘤进展中骨髓细胞的理解，并阐明了涉及细胞招募、极化和激活的许多关键调节机制。另一方面，这种范式不包括肿瘤驻留骨髓细胞表型的复杂性（IHC 只能测量每个样本的 1 或 2 个标记物）及其在不利的肿瘤微环境中可能存在的不同功能。在这里，我们检查了定义人类肿瘤浸润性骨髓细胞亚群的标准，并对癌症中的人类骨髓细胞命名法进行了全面和批判性的回顾。我们还强调了新的证据，描述了它们对癌症发病机制的贡献，这些证据基于临床研究的证据，必要时与小鼠研究进行比较。然后，我们回顾了人类肿瘤调节骨髓细胞的机制以及如何针对这些机制进行治疗。
Our current understanding of human tumor-resident myeloid cells is, for the most part, based on a large body of work in murine models or studies enumerating myeloid cells in patient tumor samples using immunohistochemistry (IHC). This has led to the establishment of the theory that, by and large, tumor-resident myeloid cells are either “protumor” M2 macrophages or myeloid-derived suppressor cells (MDSC). This concept has accelerated our understanding of myeloid cells in tumor progression and enabled the elucidation of many key regulatory mechanisms involved in cell recruitment, polarization, and activation. On the other hand, this paradigm does not embrace the complexity of the tumor-resident myeloid cell phenotype (IHC can only measure 1 or 2 markers per sample) and their possible divergent function in the hostile tumor microenvironment. Here, we examine the criteria that define human tumor-infiltrating myeloid cell subsets and provide a comprehensive and critical review of human myeloid cell nomenclature in cancer. We also highlight new evidence characterizing their contribution to cancer pathogenesis based on evidence derived from clinical studies drawing comparisons with murine studies where necessary. We then review the mechanisms in which myeloid cells are regulated by tumors in humans and how these are being targeted therapeutically.