Key role of tumor-associated macrophages in the progression and metastasis of tumors

• Irina M. Bogdanova
• Marina N. Boltovskaya
• Rakhmilevich A.L.
• Ksenia A. Artemieva

Abstract

Tumor-associated macrophages (TAM), the predominant leukocyte subclass in solid tumors, show high degree of phenotypic and functional heterogeneity under the influence of the local tumor microenvironment. TAM with antiinflammatory and protumorogenic activity modulate the microenvironment, promote tumor growth, invasion of tissue surrounding the tumor and metastasis to distant sites. They promote angiogenesis, tumor resistance to chemotherapy and radiotherapy and provide a supportive environment for the tumor to avoid immune surveillance. In tumor sites, TAM usually are alternatively activated or M2 macrophages secreting anti-inflammatory cytokines, interleukin (IL) -10, prostaglandin E2 and expressing CD206- and CD163-receptors, as well as CCL2-, CCL17- and CCL22-chemokines involved in attracting regulatory T-cells (Treg). Data from clinical and experimental studies suggest a high TAM density in the tumor with an unfavorable prognosis for patients. The use of TAM as therapeutic targets in many types of tumors is an important strategy based on the selection of agents that either inhibit the attraction of TAM in the primary tumors and metastatic sites or convert protumor TAM to antitumor effector cells.

Keywords:carcinogenesis; tumor-associated macrophages; immunosupression; regulatory factors; immunotherapy; review

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