TY - JOUR T1 - Metformin Prevents Peritoneal Dissemination <em>via</em> Immune-suppressive Cells in the Tumor Microenvironment JF - Anticancer Research JO - Anticancer Res SP - 4699 LP - 4709 DO - 10.21873/anticanres.13652 VL - 39 IS - 9 AU - TAKANORI HIRAYAMA AU - YASUHIRO NAGATA AU - MIKAKO NISHIDA AU - MITSUTOSHI MATSUO AU - SHINICHIRO KOBAYASHI AU - AKIRA YONEDA AU - KENGO KANETAKA AU - HEIICHIRO UDONO AU - SUSUMU EGUCHI Y1 - 2019/09/01 UR - http://ar.iiarjournals.org/content/39/9/4699.abstract N2 - Background/Aim: Metformin, a drug for type 2 diabetes, also exerts anticancer effects. This study addressed the immunological effects of metformin on peritoneal dissemination. Materials and Methods: We developed a mouse model of peritoneal dissemination via intraperitoneal injection of RLmale1, an X-ray-induced leukemia cell line, into BALB/c mice. Cell-surface markers, cytokine production, and myeloid-derived suppressor cells (MDSCs) were examined in cells from spleen and peritoneal lavage fluid. Results: Metformin-treated mice exhibited suppressed intraperitoneal tumor growth and extended survival, and these effects were lost in mice with severe combined immunodeficiency. MDSCs induction was inhibited in metformin-treated mice. Although MDSC mobilization into the peritoneal cavity was correlated with suppression of interferon-γ production by tumor-infiltrating lymphocytes, the T-helper 1 ability of these lymphocytes was preserved in metformin-treated mice. Conclusion: Our findings demonstrate the action of metformin on both intraperitoneal tumors and immune-suppressive cells and might contribute to the development of immunotherapy against peritoneal dissemination. ER -