Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma-Reference-Cited by-同舟云学术

Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma

Published:2021-09-08 Issue:10 Volume:218 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Paillet Juliette¹²³^ORCID,Plantureux Céleste¹²³^ORCID,Lévesque Sarah¹²³^ORCID,Le Naour Julie¹²³^ORCID,Stoll Gautier¹²^ORCID,Sauvat Allan¹²^ORCID,Caudana Pamela⁴^ORCID,Tosello Boari Jimena⁴^ORCID,Bloy Norma¹²³^ORCID,Lachkar Sylvie¹²^ORCID,Martins Isabelle¹²^ORCID,Opolon Paule⁵^ORCID,Checcoli Andrea⁶⁷^ORCID,Delaune Agathe⁸^ORCID,Robil Noémie⁸^ORCID,de la Grange Pierre⁸^ORCID,Hamroune Juliette⁹^ORCID,Letourneur Franck⁹^ORCID,Autret Gwennhael¹⁰^ORCID,Leung Patrick S.C.¹¹^ORCID,Gershwin M. Eric¹¹^ORCID,Zhu Jie S.¹²^ORCID,Kurth Mark J.¹²^ORCID,Lekbaby Bouchra¹³^ORCID,Augustin Jérémy¹⁴^ORCID,Kim Youra¹⁵^ORCID,Gujar Shashi¹⁵¹⁶¹⁷¹⁸^ORCID,Coulouarn Cédric¹⁹^ORCID,Fouassier Laura¹³^ORCID,Zitvogel Laurence²⁰^ORCID,Piaggio Eliane²¹^ORCID,Housset Chantal¹³²²^ORCID,Soussan Patrick¹³^ORCID,Maiuri Maria Chiara¹²^ORCID,Kroemer Guido¹²²³²⁴²⁵^ORCID,Pol Jonathan G.¹²^ORCID

Affiliation:

1. Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France

2. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France

3. Université Paris-Saclay, Faculté de Médecine, Kremlin-Bicêtre, France

4. Institut Curie, Paris Sciences et Lettres Research University, Institut National de la Santé et de la Recherche Médicale U932, Paris, France

5. Gustave Roussy Cancer Campus, Villejuif, France

6. Institut Curie, Paris Sciences et Lettres Research University, Paris, France

7. Institut National de la Santé et de la Recherche Médicale U900, Paris, France

8. GenoSplice Technology, Paris, France

9. Institut National de la Santé et de la Recherche Médicale U1016, Institut Cochin, Paris, France

10. Université de Paris, Paris Cardiovascular Research Centre, Institut National de la Santé et de la Recherche Médicale U970, Paris, France

11. Division of Rheumatology/Allergy and Clinical Immunology, University of California, Davis School of Medicine, Davis, CA

12. Department of Chemistry, University of California, Davis, Davis, CA

13. Institut National de la Santé et de la Recherche Médicale U938, Centre de Recherche Saint-Antoine, Sorbonne Université, Paris, France

14. Institut National de la Santé et de la Recherche Médicale U938, Centre de Recherche Saint-Antoine, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital Henri-Mondor, Département de Pathologie, Paris, France

15. Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada

16. Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada

17. Beatrice Hunter Cancer Research Institute, Halifax, Nova Scotia, Canada

18. Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada

19. Institut National de la Santé et de la Recherche Médicale, Université de Rennes 1, Chemistry, Oncogenesis Stress Signaling, UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France

20. Institut National de la Santé et de la Recherche Médicale U1015, Université Paris-Saclay, Gustave Roussy Cancer Campus, Villejuif, France

21. Centre d'Investigation Clinique Biothérapie 1428, Institut Curie, Paris, France

22. Assistance Publique-Hôpitaux de Paris, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, Department of Hepatology, Saint-Antoine Hospital, Paris, France

23. Institut Universitaire de France, Paris, France

24. Pôle de Biologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France

25. Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China

Abstract

Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract.

Funder

Association pour la lutte contre les maladies inflammatoires du foie et des voies biliaires

Dalhousie Medical Research Foundation

Canadian Cancer Society

Canadian Institutes of Health Research

Association Française d'Hépatologie

Site de Recherche intégrée sur le Cancer Cancer Research and Personalized Medicine

Seerave Foundation

Institut National du Cancer

Ligue contre le Cancer

Agence National de la Recherche

ERA-Net for Research on Rare Diseases