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Title:
significance of M2 macrophage and cell-cell interaction in human malignant tumors

Yoshihiro Komohara
Assistant Professor
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University

Abstract:
Tumor-associated macrophages (TAMs) participate in development of the tumor microenvironment by inducing angiogenesis, immunosuppression, and tumor invasion. Although many studies of the TAM population in various cancer tissues have been published, only a few described activation of the macrophage phenotype (such as M1 and M2) in human cancerous tissues.
Therefore we have investigated the significance of M2 cells in human cancers by means of immunohistochemical analysis using CD163 as one of M2-associated molecules. Since we previously demonstrated that CD163 is a useful marker to identify M2 phenotype in human paraffin-embedded samples, we’ve focused on CD163. As the results, the patients with increased infiltration of CD163 (+) TAMs showed significant poor clinical prognosis in glioma, intrahepatic cholangiocarcinoma, kidney cancer, and T-cell lymphoma, whereas no significant differences were showed in prostatic cancer, gastric cancer, esophageal cancer, and primary CNS lymphoma. From other laboratories, the correlation of increase infiltration of CD163 (+) TAMs and significant poor clinical prognosis was reported in melanoma, pancreatic cancer, and leiomyosarcoma, and notably serum soluble CD163 was significantly associated with poor clinical prognosis in patients with melanoma. CD163 (+) TAMs were significantly associated to tumor cell proliferation in high grade glioma, and in vitro co-culture study using T98G glioma cell line suggested the cell-cell interaction between macrophage and tumor cells contributes tumor cell activation and proliferation. The cell-cell interaction was up-regulated by direct cell-cell contact, and detail mechanisms are now under investigation.
In summary, although detail mechanisms have not been cleared, CD163 (+) M2 polarized TAMs are contributed to poor clinical prognosis in some kinds of human malignant tumors. Cell-cell interaction mediated direct cell-cell contact with TAMs might be associated to the malignant potential of cancer cells. The inhibition of M2 polarization by tumor-derived factors or cell-cell interaction may provide a promising approach to enhancing anticancer therapy.