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Metformin plays an antitumor role by downregulating inhibitory cells and immune checkpoint molecules while activating

Haoran Jiang1, Huandan Suo1, Liwei Gao2

  • 1Department of Surgical Oncology and Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

International Immunopharmacology
|March 30, 2023
PubMed

Insights

Metformin treatment prolonged survival in mice with breast cancer by reducing immunosuppressive cells and enhancing anti-tumor immunity. This suggests metformin

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Metformin is a widely used drug for type 2 diabetes.
  • Emerging evidence suggests potential anti-cancer properties of metformin.
  • The precise mechanisms underlying metformin's effects on breast cancer immunity require further elucidation.

Purpose of the Study:

  • To investigate the impact of metformin on breast cancer progression and survival in a murine model.
  • To analyze the immunomodulatory effects of metformin within the tumor microenvironment and spleen.

Main Methods:

  • BALB/c mice bearing 4T1 breast cancer cells were treated with metformin.
  • Survival rates and tumor sizes were monitored.
  • Flow cytometry and ELISA were employed to assess immune cell populations (M2-like macrophages, M-MDSCs, Tregs) and cytokine levels (IFN-γ, IL-10) in spleens and tumors.
  • Immune checkpoint molecule PD-1 expression on T cells was evaluated.

Main Results:

  • Metformin treatment significantly prolonged mouse survival.
  • A notable decrease in M2-like macrophages, monocytic myeloid-derived suppressor cells (M-MDSCs), and regulatory T cells (Tregs) was observed in metformin-treated mice.
  • Metformin administration led to increased levels of IFN-γ and decreased levels of IL-10.
  • Inhibition of PD-1 expression on T cells was observed following metformin treatment.

Conclusions:

  • Metformin demonstrates significant anti-tumor activity in a preclinical breast cancer model.
  • The drug enhances local anti-tumor immunity by modulating the tumor microenvironment and reducing immunosuppressive cell populations.
  • Metformin shows promise as a potential therapeutic agent for breast cancer treatment.
Keywords:
Breast cancerImmune checkpoint moleculesMetforminProtective immune response

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