The Promise of Targeting Macrophages in Cancer Therapy.
The Promise of Targeting Macrophages in Cancer Therapy.
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DOI：
10.1158/1078-0432.ccr-16-3122
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发表时间：
2017-07-01
期刊：
影响因子：
--
通讯作者：
Strober S
中科院分区：
文献类型：
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作者：
Brown JM;Recht L;Strober S
癌症治疗围绕杀死或阻止癌细胞生长的概念发展。分子靶向治疗是这一范式的现代表达。然而，越来越多地认识到，癌症为了自身的生存而选择了基质的正常细胞，这导致了肿瘤微环境（TME）可以被靶向用于有效治疗的概念。在这篇综述中，我们概述了肿瘤相关巨噬细胞（TAMs）的重要性，TME的主要组成部分，在肿瘤对癌症治疗的反应。我们讨论了巨噬细胞在伤口愈合中的正常作用，TAMs的主要表型，以及它们通过促进肿瘤血管生成和抑制抗肿瘤免疫来减弱放射和抗癌药物对癌症治疗的疗效。最后，我们回顾了许多临床前研究，这些研究表明，肿瘤对辐射和抗癌药物的反应可以得到改善，有时显着改善，通过耗尽肿瘤中的TAM或通过抑制它们从M1到M2表型的极化。这些数据清楚地支持靶向TAM与常规治疗相结合的临床试验的有效性。
Cancer therapy has developed around the concept of killing, or stopping the growth of, the cancer cells. Molecularly targeted therapy is the modern expression of this paradigm. Increasingly, however, the realization that the cancer has co-opted the normal cells of the stroma for its own survival has led to the concept that the tumor microenvironment (TME) could be targeted for effective therapy. In this Review we outline the importance of tumor associated macrophages (TAMs), a major component of the TME, in the response of tumors to cancer therapy. We discuss the normal role of macrophages in wound healing, the major phenotypes of TAMs and their role in blunting the efficacy to cancer treatment by radiation and anticancer drugs both by promoting tumor angiogenesis and by suppressing antitumor immunity. Finally we review the many preclinical studies that have shown that the response of tumors to irradiation and anticancer drugs can be improved, sometimes markedly so, by depleting TAMs from tumors or by suppressing their polarization from an M1 to an M2 phenotype. The data clearly support the validity of clinical testing of combining targeting TAMs with conventional therapy.