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Seminaire by Prof. Elisabeth Letellier, University of Luxembourg, Co-head of the Molecular Disease Mechanisms Group
Tuesday October 17, 11am, IGMM

Deciphering the heterogeneity of cancer-associated fibroblast populations in colorectal cancer

Abstract

Over the past years, cancer research has moved from a tumor-centric view towards a more holistic view of cancer, which recognizes the importance of the tumor microenvironment (TME) in tumor growth and progression. Among the cells of the TME, cancer-associated fibroblasts (CAFs) have risen to increased prominence as one of the key factors driving tumor development. Due to their heterogeneity, which is linked to different gene expression profiles and cellular functions, it is of vital importance to understand the precise mechanisms through which CAFs develop and maintain pro-tumorigenic phenotypes in patients. Using a combination of patient-derived single cell RNA-sequencing and bulk transcriptome dataset analyses, together with novel 3D organotypic co-culture cell assays and relevant in CRC in vivo models, we identified CAF subtypes that are linked to tumor growth and immune suppression. The therapeutic importance of targeting pro-tumorigenic fibroblasts in CRC will be discussed during this seminar.

References:

IL1R1+ cancer-associated fibroblasts drive tumor development and immunosuppression in colorectal cancer.
Koncina E, Nurmik M, Pozdeev VI, Gilson C, Tsenkova M, Begaj R, Stang S, Gaigneaux A, Weindorfer C, Rodriguez F, Schmoetten M, Klein E, Karta J, Atanasova VS, Grzyb K, Ullmann P, Halder R, Hengstschläger M, Graas J, Augendre V, Karapetyan YE, Kerger L, Zuegel N, Skupin A, Haan S, Meiser J, Dolznig H, Letellier E. Nat Commun. 2023 Jul 17;14(1):4251. doi: 10.1038/s41467-023-39953-w.

The gut microbial metabolite formate exacerbates colorectal cancer progression.
Ternes D, Tsenkova M, Pozdeev VI, Meyers M, Koncina E, Atatri S, Schmitz M, Karta J, Schmoetten M, Heinken A, Rodriguez F, Delbrouck C, Gaigneaux A, Ginolhac A, Nguyen TTD, Grandmougin L, Frachet-Bour A, Martin-Gallausiaux C, Pacheco M, Neuberger-Castillo L, Miranda P, Zuegel N, Ferrand JY, Gantenbein M, Sauter T, Slade DJ, Thiele I, Meiser J, Haan S, Wilmes P, Letellier E. Nat Metab. 2022 Apr;4(4):458-475. doi: 10.1038/s42255-022-00558-0.

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With financial support from INCa, DGOS, and Inserm