Mapping stromal heterogeneity and immunosuppression in breast cancer

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• Fatima Mechta-Grigoriou
• Thursday 14 December 2023, 11:30-12:30
• CRUK CI Lecture Theatre.

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Please note change of time to 11.30-12.30

Abstract In the last years, we demonstrated the plasticity of cancer-associated fibroblasts (CAF) through reciprocal crosstalk with both cancer and immune cells, and identified distinct identities and multiple roles of CAF populations in metastatic spread and immunosuppression (Pelon, Nat Commun, 2020; Bonneau Br. Cancer Res., 2020; Magagna, Cancers, 2021; Mieulet, Sci. Reports, 2021). Because of the dual (pro-metastatic and immunosuppressive) function of the FAP CAF population (called CAF -S1), we hypothesized that this population is more complex than initially thought. We performed single-cell RNA sequencing of more than 18 000 CAF -S1 isolated from breast cancer, generating one of the most exhaustive studies of this CAF population in human cancer (Kieffer, Cancer Discovery, 2020; Mhaidly, Semin. Immunol., 2020; Mhaidly, Immunol Rev., 2021). We identified 8 FAP CAF / CAF -S1 cellular clusters and demonstrated that the immunosuppressive activity of CAF -S1 is restricted to specific clusters, which also predict immunotherapy resistance (Kieffer, Cancer Discovery, 2020; Peltier, Sem. Cancer Biol., 2022; Mhaidly, Cancer Cell, 2022). Finally, we have recently evaluated the impact of chemotherapy on CAF populations (Licaj, Under Review) and defined FAP + CAF / CAF -S1 plasticity and spatial topology in breast cancer (Croizer, Under Review). Interestingly, we recently showed that these fibroblast populations can also be observed in chronic fibrotic disease, showing that our findings are not restricted to cancer but can be widely extended to other pathologies (Cohen, Nat Commun, In press).

Recent publications Cohen, Nature Communications, In press Kieffer Y., Cancer Discovery, 2020 May 20:CD-19-1384 Pelon F., Nature Communications, 2020 Jan 21;11(1):404 Bonneau C., Breast Cancer Research, 2020 Jul 14;22(1):76 Gentric G., Cell Metabolism, 2019, 29, 156-173 Costa A., Cancer Cell, 2018 Mar 12;33(3):463-479.e10 Givel AM, Nature Communications, 2018, Mar 13;9(1):1056

This talk is part of the Cancer Research UK Cambridge Institute (CRUK CI) Seminars in Cancer series.

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