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Updated: Jan 19, 2026
Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
Metformin Prevents Peritoneal Dissemination via Immune-suppressive Cells in the Tumor Microenvironment
Takanori Hirayama1, Yasuhiro Nagata2,3, Mikako Nishida4
1Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
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.
Insights
Metformin, a type 2 diabetes drug, suppresses peritoneal tumor growth and extends survival by inhibiting immune-suppressive myeloid-derived suppressor cells (MDSCs). This suggests metformin
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Metformin, a common type 2 diabetes medication, demonstrates potential anticancer properties.
- Peritoneal dissemination presents a significant challenge in various cancers, often associated with immune suppression.
Purpose of the Study:
- To investigate the immunological effects of metformin on peritoneal dissemination.
- To elucidate metformin's impact on tumor growth, immune cell populations, and cytokine profiles in a preclinical model.
Main Methods:
- A mouse model of peritoneal dissemination was established using RLmale1 leukemia cells.
- Analysis included cell-surface markers, cytokine production, and myeloid-derived suppressor cells (MDSCs) in spleen and peritoneal lavage fluid.
Main Results:
- Metformin treatment suppressed tumor growth and improved survival in mice with peritoneal dissemination.
- Metformin inhibited the induction of MDSCs and preserved T-helper 1 cell function.
- Tumor growth suppression by metformin was dependent on an intact immune system.
Conclusions:
- Metformin exhibits immunomodulatory effects against peritoneal tumors by targeting immune-suppressive cells.
- These findings support the potential of metformin as an adjunct therapy for peritoneal dissemination, possibly enhancing immunotherapy outcomes.
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