Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.
FEBS J. 2018 Feb;285(4):777-787. doi: 10.1111/febs.14202. Epub 2017 Sep 6.
Tumor-associated macrophages (TAM) are by now established as important regulators of tumor progression by impacting on tumor immunity, angiogenesis, and metastasis. Hence, a multitude of approaches are currently pursued to intervene with TAM's protumor activities, the most advanced of which being a blockade of macrophage-colony stimulating factor (M-CSF)/M-CSF receptor (M-CSFR) signaling. M-CSFR signaling largely impacts on the differentiation of macrophages, including TAM, and hence strongly influences the numbers of these cells in tumors. However, a repolarization of TAM toward a more antitumor phenotype may be more elegant and may yield stronger effects on tumor growth. In this respect, several aspects of TAM behavior could be altered, such as their intratumoral localization, metabolism and regulatory pathways. Intervention strategies could include the use of small molecules but also new generations of biologicals which may complement the current success of immune checkpoint blockers. This review highlights current work on the search for new therapeutic targets in TAM.
肿瘤相关巨噬细胞（TAM）通过影响肿瘤免疫、血管生成和转移，现已被确立为肿瘤进展的重要调节因子。因此，目前正在尝试多种方法来干预 TAM 的促肿瘤活性，其中最先进的方法是阻断巨噬细胞集落刺激因子（M-CSF）/M-CSF 受体（M-CSFR）信号。M-CSFR 信号对巨噬细胞（包括 TAM）的分化有很大影响，因此强烈影响肿瘤中这些细胞的数量。然而，TAM 向更抗肿瘤表型的重极化可能更优雅，并可能对肿瘤生长产生更强的影响。在这方面，可以改变 TAM 行为的几个方面，例如它们在肿瘤内的定位、代谢和调节途径。干预策略可能包括使用小分子，也可能包括新一代的生物制剂，这些制剂可能会补充免疫检查点抑制剂目前的成功。这篇综述强调了目前在 TAM 中寻找新治疗靶点的工作。
