Clin Cancer Res: The effect of small doses of metformin on the immune microennourage of esophageal cancer tumors.

Tumor immune microennourage (TIME) has an important effect on the response of cancer immunotherapy using immunos checkpoint inhibitors.
specifically, "immersion exclusion" / "cold" TIME can indicate adverse reactions.
drug metformin may affect the anti-tumor immunity of esophageal squamous cell carcinoma (ESCC).
In a Phase II clinical trial of low-dose metformin (250 mg/day) therapy, the researchers analyzed samples of esophageal squamous cancer before and after the paired treatment to assess the activity of direct resistance to ESCC and TIME reprogramming.
, the ESCC mouse model was treated in small doses of metformin (50 mg/kg/day) for short-term (1 week) or long-term (12 weeks).
in clinical trials, small doses of metformin did not affect cell proliferation and apoptosis of ESCC tumors (assessed according to Ki67 and caspase-3).
but metformin treatment has reprogrammed TIME to "inflamed", increasing the number of immersion CD8-T lymphocytes and CD20-B lymphocytes.
addition, an increase in tumor-suppressing (CD11c-plus) macrophages and a decrease in tumor-promoting (CD163-plus) macrophages were observed.
, metformin enhances macrophage-mediated ESCC cell phagocytoscide.
In ESCC mice, metformin was reprogrammed in a similar way to reprogramming TIME in humans, but long-term treatment further shifted TIME to an active state (e.g., CD4-FoxP3-regulated T-cell reduction) and inhibited ESCC growth.
in both humans and mice, metformin triggered AMPK activation and STAT3 inactivation, altering the synthesis of cytokines in immune cells (e.g. TNF alpha, IFN, and IL-10).
, low-dose metformin can reprogram TIME to an active state and may be a suitable immunosystay regulator, which deserves further study.
.