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Role of tumor-associated macrophages in the progression of hepatocellular carcinoma

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Abstract

Recent studies have shown that the tumor microenvironment plays an important role in cancer progression. Tumor-associated macrophages (TAMs), in particular, have been found to be associated with tumor progression. Macrophages have multiple biological roles, including antigen presentation, target cell cytotoxicity, removal of foreign bodies, tissue remodeling, regulation of inflammation, induction of immunity, thrombosis, and endocytosis. Recent immunological studies have identified two distinct states of polarized macrophage activation: the classically activated (M1) and the alternatively activated (M2) macrophage phenotypes. Bacterial moieties such as lipopolysaccharides and the Th1 cytokine interferon-γ polarize macrophages toward the M1 phenotype. The M2 polarization was discovered as a response to the Th2 cytokine interleukin-4. In general, M2 macrophages exert immunoregulatory activity, participate in polarized Th2 responses, and aid tumor progression. TAMs have recently been found to play an important role in hepatocellular carcinoma (HCC) progression. Based on the properties of TAMs, obtained from pathological examination of resected specimens, we have identified new therapeutic approaches, involving the targeting of TAMs with adjuvant therapy after hepatic resection for HCC. This review discusses the roles of TAM in HCC progression and the possibility of new therapies targeting TAMs.

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Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Ken Shirabe, Yohei Mano, Jun Muto, Rumi Matono, Takashi Motomura, Takeo Toshima, Kazuki Takeishi, Hidekaki Uchiyama, Tomoharu Yoshizumi, Akinobu Taketomi, Masaru Morita, Shunichi Tsujitani & Yoshihiko Maehara

  2. Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan

    Yoshihisa Sakaguchi

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  1. Ken Shirabe
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Shirabe, K., Mano, Y., Muto, J. et al. Role of tumor-associated macrophages in the progression of hepatocellular carcinoma. Surg Today 42, 1–7 (2012). https://doi.org/10.1007/s00595-011-0058-8

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