Open AccessAutoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma
Author(s) -
Juliette Paillet,
Céleste Plantureux,
Sophie Lévesque,
Julie Le Naour,
Gautier Stoll,
Allan Sauvat,
Pamela Caudana,
Jimena Tosello,
Norma Bloy,
Sylvie Lachkar,
Isabelle Martins,
Paule Opolon,
Andrea Checcoli,
Agathe Delaune,
Noémie Robil,
Pierre de la Grange,
Juliette Hamroune,
Franck Letourneur,
Gwennhaël Autret,
Patrick S.C. Leung,
M. Eric Gershwin,
Jie Zhu,
Mark J. Kurth,
Bouchra Lekbaby,
Jérémy Augustin,
Youra Kim,
Shashi Gujar,
Cédric Coulouarn,
Laura Fouassier,
Laurence Zitvogel,
Eliane Piaggio,
Chantal Housset,
Patrick Ben Soussan,
Maria Chiara Maiuri,
Guido Kroemer,
Jonathan Pol
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20200853
Subject(s) - immunosurveillance , autoimmunity , context (archaeology) , biliary tract , immunology , primary sclerosing cholangitis , biology , cancer research , medicine , immune system , pathology , disease , paleontology
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.