Beneficial autoimmunity links primary biliary cholangitis to the avoidance of cholangiocarcinoma

Jonathan G Pol; Juliette Paillet; Céleste Plantureux; Guido Kroemer

doi:10.1080/2162402X.2021.1968595

Beneficial autoimmunity links primary biliary cholangitis to the avoidance of cholangiocarcinoma

Oncoimmunology. 2021 Sep 11;10(1):1968595. doi: 10.1080/2162402X.2021.1968595. eCollection 2021.

Authors

Jonathan G Pol^{1

2}, Juliette Paillet^{1

2

3}, Céleste Plantureux^{1

2

3}, Guido Kroemer^{1

2

4

5

6

7}

Affiliations

¹ Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université, Paris, France.
² Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
³ Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.
⁴ Institut Universitaire de France, Paris, France.
⁵ Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
⁶ Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.
⁷ Department of Women's and Children's Health, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.

Abstract

It has been an open conundrum why primary sclerosing cholangitis (PSC) is a major risk factor for developing cholangiocarcinoma (CAA), while primary biliary cholangitis (PBC) is not. In mouse models of PSC and PBC, it turned out that the latter condition, an autoimmune disease affecting the bile ducts, reduces transgene-induced cholangiocarcinogenesis, as well as the progression of subcutaneously implanted CCA. This CCA-delaying effect is lost upon depletion of T lymphocytes and involves tumor infiltration by T cell clonotypes that are also found in PBC lesions. Hence, organ-specific autoimmunity may improve immunosurveillance.

Keywords: Cancer immunosurveillance; T lymphocytes; autoimmunity; cholangiocarcinoma; primary biliary cholangitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autoimmunity
Bile Duct Neoplasms* / etiology
Bile Ducts, Intrahepatic / pathology
Cholangiocarcinoma* / pathology
Cholangitis, Sclerosing* / pathology
Liver Cirrhosis, Biliary* / pathology
Mice

Grants and funding

This study was supported by the Association pour la lutte contre les maladies inflammatoires du foie et des voies biliaires (albi). JGP is supported by the Association Française d’Hépatologie (AFEF); SIRIC Cancer Research and Personalized Medicine (CARPEM); Multi-Organism Institute (ITMO) Aviesan Cancer (National Alliance for Life Sciences and Health), and Institut National du Cancer (INCa). GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association “Ruban Rose”; Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Programme on Rare Diseases (EJPRD); Gustave Roussy Odyssea, the European Union Horizon 2020 Projects Oncobiome and Crimson; Fondation Carrefour; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LabEx Immuno-Oncology [ANR-18-IDEX-0001]; the Leducq Foundation; the RHU Torino Lumière; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM). This study contributes to the IdEx Université de Paris ANR-18-IDEX-0001.