학술논문
Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma
Document Type
article
Author
Paillet, Juliette; Plantureux, Céleste; Lévesque, Sarah; Le Naour, Julie; Stoll, Gautier; Sauvat, Allan; Caudana, Pamela; Boari, Jimena Tosello; Bloy, Norma; Lachkar, Sylvie; Martins, Isabelle; Opolon, Paule; Checcoli, Andrea; Delaune, Agathe; Robil, Noémie; de la Grange, Pierre; Hamroune, Juliette; Letourneur, Franck; Autret, Gwennhael; Leung, Patrick SC; Gershwin, M Eric; Zhu, Jie S; Kurth, Mark J; Lekbaby, Bouchra; Augustin, Jérémy; Kim, Youra; Gujar, Shashi; Coulouarn, Cédric; Fouassier, Laura; Zitvogel, Laurence; Piaggio, Eliane; Housset, Chantal; Soussan, Patrick; Maiuri, Maria Chiara; Kroemer, Guido; Pol, Jonathan G
Source
Journal of Experimental Medicine. 218(10)
Subject
Language
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.