What is it about?
Collapsed tumor vessels inhibits CD8T cell migration to tumor. We found that immuno-therapy of Metformin and anti-PD-1 Ab normalize the vessels via IFNγ produced from CD8T cells, promoting entry of the immune cells. The increased CD8T cells further normalize tumor vessels. Thus, there is a IFNγ-mediated crosstalk of CD8T cells with tumor vessels by which sustained anti-tumor immunity is maintained in the tumor microenvironment.
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Why is it important?
Tumor blood vessels are highly leaky in the structure and have poor blood perfusion, which hampers infiltration and function of CD8T cells within tumor. Normalizing tumor vessels is thus thought to be important in promoting the flux of immune T cells and enhancing anti-tumor immunity. We found that combination therapy with Metformin and anti-PD-1 Ab normalize tumor vessels to promote infiltration of CD8T cells to tumor, leading to the sustained anti-tumor immunity.
Perspectives
There is much debate regarding the anti-tumor effect mechanism of the diabetes drug metformin. In this study, we found that combination therapy with metformin and anti-PD-1 antibody produced large numbers of IFNγ-producing CD8T cells, and that this IFNγ normalized tumor blood vessels, promoting further influx of CD8T cells into the tumor. I believe that we have uncovered a new mechanism by which metformin induces anti-tumor immunity.
Heiichiro Udono
Okayama Daigaku
Read the Original
This page is a summary of: Metformin synergizes with PD-1 blockade to promote normalization of tumor vessels via CD8T cells and IFNγ, Proceedings of the National Academy of Sciences, July 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2404778121.
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