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The role of macrophage phenotype in regulating the response to radiation therapy

Published:November 20, 2017DOI:https://doi.org/10.1016/j.trsl.2017.11.002
      Increasing experimental and clinical evidence has revealed a critical role for myeloid cells in the development and progression of cancer. The ability of monocytes and macrophages to regulate inflammation allows them to manipulate the tumor microenvironment to support the growth and development of malignant cells. Recent studies have shown that macrophages can exist in several functional states depending on the microenvironment they encounter in the tissue. These functional phenotypes influence not only the genesis and propagation of tumors, but also the efficacy of cancer therapies, particularly radiation. Early classification of the macrophage phenotypes, or “polarization states,” identified 2 major states, M1 and M2, that have cytotoxic and wound repair capacity, respectively. In the context of tumors, classically activated or M1 macrophages driven by interferon-gamma support antitumor immunity while alternatively activated or M2 macrophages generated in part from interleukin-4 exposure hinder antitumor immunity by suppressing cytotoxic responses against a tumor. In this review, we discuss the role that the functional phenotype of a macrophage population plays in tumor development. We will then focus specifically on how macrophages and myeloid cells regulate the tumor response to radiation therapy.

      Abbreviations:

      RT (radiation therapy), IFN-γ (interferon-γ), TLR (toll-like receptor), STAT (signal transducer and activator of transcription), NF-κB (nuclear factor-κB), CXCLs (C-X-C motif ligands), CCLs (C-C motif ligands), iNOS (inducible nitric oxide synthase), IL (interleukin), TNF (tumor necrosis factor), Arg-1 (arginase-1), VEGF (vascular endothelial growth factor), CSF1 (colony stimulating factor 1), TAMs (tumor-associated macrophages), M-CSF (macrophage colony-stimulating factor), PD-1 (programmed death-1), HIF-1α (hypoxia-inducible factor-1α), MMP (matrix metalloproteinase), DAMP (damage-associated molecular pattern), HMGB1 (high mobility group protein box 1), CRT (calreticulin), STING (stimulator of interferon genes), DCs (dendritic cells), Gy (Gray), miRNA (microRNA), MDSCs (myeloid-derived suppressor cells), IDO (indoleamine-2,2-dioxygenase), GATA3 (GATA-binding protein 3)
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