Tumor metastasis is a major contributor to the death of cancer patients. It is driven not only by the intrinsic alterations in tumor cells, but also by the implicated cross-talk between cancer cells and their altered microenvironment components. Tumor-associated macrophages (TAMs) are the key cells that create an immunosuppressive tumor microenvironment (TME) by producing cytokines, chemokines, growth factors, and triggering the inhibitory immune checkpoint proteins release in T cells. In doing so, TAMs exhibit important functions in facilitating a metastatic cascade of cancer cells and, meanwhile, provide multiple targets of certain checkpoint blockade immunotherapies for opposing tumor progression. In this article, we summarize the regulating networks of TAM polarization and the mechanisms underlying TAM-facilitated metastasis. Based on the overview of current experimental evidence dissecting the critical roles of TAMs in tumor metastasis, we discuss and prospect the potential applications of TAM-focused therapeutic strategies in clinical cancer treatment at present and in the future.

中文翻译：

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肿瘤转移中与肿瘤相关的巨噬细胞：生物学作用和临床治疗应用。

肿瘤转移是导致癌症患者死亡的主要因素。它不仅受到肿瘤细胞内在变化的驱动，而且还受到癌细胞与其变化的微环境组分之间牵连的串扰的驱动。肿瘤相关巨噬细胞（TAM）是通过产生细胞因子，趋化因子，生长因子并触发抑制性免疫检查点蛋白在T细胞中释放而创建免疫抑制性肿瘤微环境（TME）的关键细胞。这样做，TAM在促进癌细胞的转移级联中显示出重要的功能，同时，为某些对抗肿瘤进展的检查点封锁免疫疗法提供了多个靶点。在本文中，我们总结了TAM极化的调控网络以及TAM促进转移的潜在机制。