Elliott Louise A, Doherty Glen A, Sheahan Kieran, Ryan Elizabeth J
Centre for Colorectal Disease, St. Vincent's University Hospital, School of Medicine, University College Dublin , Dublin , Ireland.
Front Immunol. 2017 Feb 6;8:86. doi: 10.3389/fimmu.2017.00086. eCollection 2017.
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.
目前，我们对人类肿瘤驻留髓系细胞的理解，在很大程度上基于在小鼠模型中开展的大量研究工作，或使用免疫组织化学（IHC）对患者肿瘤样本中的髓系细胞进行计数的研究。这导致了一种理论的建立，即总体而言，肿瘤驻留髓系细胞要么是“促肿瘤”的M2巨噬细胞，要么是髓系来源的抑制细胞（MDSC）。这一概念加速了我们对髓系细胞在肿瘤进展中的理解，并使得阐明许多参与细胞募集、极化和激活的关键调控机制成为可能。另一方面，这种范式并未涵盖肿瘤驻留髓系细胞表型的复杂性（IHC每个样本只能检测1种或2种标志物）及其在恶劣肿瘤微环境中可能存在的不同功能。在此，我们研究了定义人类肿瘤浸润髓系细胞亚群的标准，并对癌症中人类髓系细胞命名法进行了全面且批判性的综述。我们还根据临床研究证据，突出了它们对癌症发病机制贡献的新证据，并在必要时与小鼠研究进行比较。然后，我们回顾了人类肿瘤对髓系细胞的调控机制，以及针对这些机制的治疗靶点。
