1. Erythropoietin induces tumour progression and CD39 expression on immune cells in a preclinical model of triple‐negative breast cancer.
- Author
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Bessoles, Stéphanie, Chiron, Andrada, Sarrabayrouse, Guillaume, De La Grange, Pierre, Abina, Amine M., and Hacein‐Bey‐Abina, Salima
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TRIPLE-negative breast cancer , *REGULATORY T cells , *ERYTHROPOIETIN , *ANIMAL models in research , *T cells - Abstract
The adverse effects observed in some cancer patients treated with erythropoiesis‐stimulating agents such as erythropoietin (EPO) might be due to the latter's well‐known immunosuppressive functions. Here, we used a mouse model of syngeneic triple‐negative breast cancer to explore EPO's immunomodulatory role in a tumour setting. Our results showed that EPO treatment promotes tumour growth, exacerbates the ‘immune desert’, and results in a ‘cold tumour’. EPO treatment changed the immune cell distribution in peripheral blood, secondary lymphoid organs, and the tumour microenvironment (TME). Our in‐depth analysis showed that EPO mainly impacts CD4 T cells by accelerating their activation in the spleen and thus their subsequent exhaustion in the TME. This process is accompanied by a general elevation of CD39 expression by several immune cells (notably CD4 T cells in the tumour and spleen), which promotes an immunosuppressive TME. Lastly, we identified a highly immunosuppressive CD39+ regulatory T cell population (ICOS+, CTLA4+, Ki67+) as a potential biomarker of the risk of EPO‐induced tumour progression. EPO displays pleiotropic immunosuppressive functions and enhances mammary tumour progression in mice. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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