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 S, Chiron A, Sarrabayrouse G, De La Grange P, Abina AM, and Hacein-Bey-Abina S
- Subjects
- Animals, Female, Mice, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes drug effects, Cell Line, Tumor, Disease Models, Animal, Disease Progression, Mammary Neoplasms, Experimental immunology, Mammary Neoplasms, Experimental drug therapy, Mammary Neoplasms, Experimental pathology, Mice, Inbred BALB C, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory drug effects, Antigens, CD metabolism, Apyrase metabolism, Erythropoietin pharmacology, Triple Negative Breast Neoplasms immunology, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms pathology, Tumor Microenvironment immunology, Tumor Microenvironment drug effects
- 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., (© 2024 The Author(s). Immunology published by John Wiley & Sons Ltd.)- Published
- 2024
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