RT Journal Article SR Electronic T1 Metformin Prevents Peritoneal Dissemination via Immune-suppressive Cells in the Tumor Microenvironment JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 4699 OP 4709 DO 10.21873/anticanres.13652 VO 39 IS 9 A1 TAKANORI HIRAYAMA A1 YASUHIRO NAGATA A1 MIKAKO NISHIDA A1 MITSUTOSHI MATSUO A1 SHINICHIRO KOBAYASHI A1 AKIRA YONEDA A1 KENGO KANETAKA A1 HEIICHIRO UDONO A1 SUSUMU EGUCHI YR 2019 UL http://ar.iiarjournals.org/content/39/9/4699.abstract AB 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.