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Journal articles
Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer
Yann Kieffer
1
Hocine Rachid Hocine
1
Géraldine Gentric
1
Floriane Pelon
1
Charles Bernard
1
Brigitte Bourachot
1
Sonia Lameiras
1, 2
Luca Albergante
3
Claire Bonneau
1
Alice Guyard
4
Karin Tarte
5
Andrei Zinovyev
1
Sylvain Baulande
1
Gérard Zalcman
4
Anne Vincent-Salomon
1
Fatima Mechta-Grigoriou
1, *
Yann Kieffer 1
Author
Hocine Rachid Hocine 1
Author
Géraldine Gentric 1
Author IdHAL : geraldine-gentric ORCID : https://orcid.org/0000-0002-7558-8705
Floriane Pelon 1
Author
Charles Bernard 1
Author
Brigitte Bourachot 1
Author
Sonia Lameiras 1, 2
Author
Luca Albergante 3
Author
Claire Bonneau 1
Author
Alice Guyard 4
Author
Karin Tarte 5
Author
Andrei Zinovyev 1
Author IdHAL : andrei-zinovyev
Sylvain Baulande 1
Author
Gérard Zalcman 4
Author
Anne Vincent-Salomon 1
Author
Fatima Mechta-Grigoriou 1
Correspondent author
1
Institut Curie [Paris] ( 26 rue d'Ulm - 75248 Paris - France)
3
Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe (26 rue d'Ulm - 75248 Paris cedex 05 - France)
- Institut Curie [Paris] ( 26 rue d'Ulm - 75248 Paris - France)
- MINES ParisTech - École nationale supérieure des mines de Paris (60, boulevard Saint-Michel 75006 Paris - France)
- PSL - Université Paris sciences et lettres (60 rue Mazarine 75006 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U900 (101, rue de Tolbiac, 75013 Paris - France)
4
CIC - CHU Bichat (Gh Xavier Bichat - Claude Bernard PARIS VII 46, Rue Henri Huchard 75018 PARIS - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : CIC7 (101, rue de Tolbiac, 75013 Paris - France)
5
MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer (INSERM UMR1236, Campus Santé, Bât 2, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France - France)
- UR1 - Université de Rennes 1 (2 rue du Thabor - CS 46510 - 35065 Rennes cedex - France)
- UNIV-RENNES - Université de Rennes (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1236 (101, rue de Tolbiac, 75013 Paris - France)
- Biosit : Biologie - Santé - Innovation Technologique - Structure Fédérative de Recherche en Biologie et Santé de Rennes (Université Rennes 1 - Campus Santé Villejean - 2, avenue Professeur Léon Bernard 35043 Rennes cedex - France)
Abstract : A subset of Cancer-Associated Fibroblasts (FAP+/CAF-S1) mediates immunosuppression in breast cancers (BC), but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 19000 single CAF-S1 fibroblasts from BC. We validate the 5 most abundant clusters by flow cytometry and in silico analyses in other cancer types, highlighting their relevance. Myofibroblasts from clusters 0 and 3, characterized by extra-cellular matrix proteins and TGFB signaling respectively, are indicative of primary resistance to immunotherapies. Cluster 0/ecm-myCAF up-regulates PD-1 and CTLA-4 protein levels in regulatory T lymphocytes (Tregs), which in turn increases CAF-S1 cluster 3/TGFB-myCAF cellular content. Thus, our study highlights a positive feedback loop between specific CAF-S1 clusters and Tregs and uncovers their role in immunotherapy resistance.
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Journal articles
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https://hal.archives-ouvertes.fr/hal-02890211
Contributor : Laurent Jonchère <>
Submitted on : Thursday, July 9, 2020 - 3:56:15 PM
Last modification on : Wednesday, January 20, 2021 - 9:57:20 AM
Long-term archiving on: : Monday, November 30, 2020 - 6:09:16 PM
Contributor : Laurent Jonchère <>
Submitted on : Thursday, July 9, 2020 - 3:56:15 PM
Last modification on : Wednesday, January 20, 2021 - 9:57:20 AM
Long-term archiving on: : Monday, November 30, 2020 - 6:09:16 PM
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Identifiers
- HAL Id : hal-02890211, version 1
- DOI : 10.1158/2159-8290.CD-19-1384
- PUBMED : 32434947
Collections
UR1-UFR-SVE | ENSMP | MICMAC | UNIV-RENNES | UNIV-RENNES1 | BIOSIT | FNCLCC | U917 | INSTITUT-TELECOM | ENSMP_CBIO | CURIE | PARISTECH | PSL | PRAIRIE-IA
Citation
Yann Kieffer, Hocine Rachid Hocine, Géraldine Gentric, Floriane Pelon, Charles Bernard, et al.. Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer. Cancer Discovery, American Association for Cancer Research, 2020, 10 (9), pp.1330-1351. ⟨10.1158/2159-8290.CD-19-1384⟩. ⟨hal-02890211⟩
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