Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma

Juliette Paillet; Céleste Plantureux; Sarah Lévesque; Julie Le Naour; Gautier Stoll; Allan Sauvat; Pamela Caudana; Jimena Tosello Boari; Norma Bloy; Sylvie Lachkar; Isabelle Martins; Paule Opolon; Andrea Checcoli; Agathe Delaune; Noémie Robil; Pierre de la Grange; Juliette Hamroune; Franck Letourneur; Gwennhael Autret; Patrick S.C. Leung; M. Eric Gershwin; Jie S. Zhu; Mark J. Kurth; Bouchra Lekbaby; Jérémy Augustin; Youra Kim; Shashi Gujar; Cédric Coulouarn; Laura Fouassier; Laurence Zitvogel; Eliane Piaggio; Chantal Housset; Patrick Soussan; Maria Chiara Maiuri; Guido Kroemer; Jonathan G. Pol

doi:10.1084/jem.20200853

Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma

Juliette Paillet, Céleste Plantureux, Sarah Lévesque, Julie Le Naour, Gautier Stoll, Allan Sauvat, Pamela Caudana, Jimena Tosello Boari, Norma Bloy, Sylvie Lachkar, Isabelle Martins, Paule Opolon, Andrea Checcoli, Agathe Delaune, Noémie Robil, Pierre de la Grange, Juliette Hamroune, Franck Letourneur, Gwennhael Autret, Patrick S.C. LeungM. Eric Gershwin, Jie S. Zhu, Mark J. Kurth, Bouchra Lekbaby, Jérémy Augustin, Youra Kim, Shashi Gujar, Cédric Coulouarn, Laura Fouassier, Laurence Zitvogel, Eliane Piaggio, Chantal Housset, Patrick Soussan, Maria Chiara Maiuri, Guido Kroemer, Jonathan G. Pol

Medicine

Résultat de recherche: Article › examen par les pairs

27 Citations (Scopus)

Résumé

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.

Langue d'origine	English
Numéro d'article	e20200853
Journal	Journal of Experimental Medicine
Volume	218
Numéro de publication	10
DOI	https://doi.org/10.1084/jem.20200853
Statut de publication	Published - sept. 8 2021

Note bibliographique

Funding Information:
J. Paillet is supported by the Association pour la lutte contre les maladies inflammatoires du foie et des voies biliaires. S. Gujar is supported by Dalhousie Medical Research Foundation, Canadian Cancer Society, and Canadian Institutes of Health Research. J.G. Pol is supported by the Association Française d’Hépatologie; Site de Recherche intégrée sur le Cancer Cancer Research and Personalized Medicine; Seerave Foundation; Multi-Organism Institute (ITMO) Aviesan Cancer (National Alliance for Life Sciences and Health); and Institut National du Cancer. G. Kroemer is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; Agence National de la Recherche under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer; Cancéropôle Ile-de-France; Chancellerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale; a donation by Elior; European Research Area Network on Cardiovascular Diseases (MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project On-cobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051), Institut National du Cancer; Inserm Program Heterogeneity of Tumors & Ecosystem; Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology; the Recherche Hospitalo-Universitaire Torino Lumière; the Seerave Foundation; the Site de Recherche intégrée sur le Cancer Stratified Oncology Cell DNA Repair and Tumor Immune Elimination; and Cancer Research and Personalized Medicine.

Funding Information:
We would like to thank Estelle Dev?vre and H?l?ne Forher-Ting (Centre d?Histologie, d?Imagerie et de Cytom?trie core facility, Cordeliers Research Center, Institut National de la Sant? et de la Recherche M?dicale [INSERM] U1138, Paris) and the staff of the histo-cytopathology core facility of the Gustave Roussy cancer campus (Villejuif, France), as well as the staff of the Genom?IC platform of the Cochin Institute (INSERM U1016, Paris) for their assistance in flow cytometry, histology, and transcriptomic analyses, respectively. We also thank Pr. Raoul Poupon for having supported this project since the very beginning. J. Paillet is supported by the Association pour la lutte contre les maladies inflammatoires du foie et des voies biliaires. S. Gujar is supported by Dalhousie Medical Research Foundation, Canadian Cancer Society, and Canadian Institutes of Health Research. J.G. Pol is supported by the Association Fran?aise d?H?patologie; Site de Recherche int?gr?e sur le Cancer Cancer Research and Personalized Medicine; Seerave Foundation; Multi-Organism Institute (ITMO) Aviesan Cancer (National Alliance for Life Sciences and Health); and Institut National du Cancer. G. Kroemer is supported by the Ligue contre le Cancer (?quipe labellis?e); Agence National de la Recherche (ANR) ? Projets blancs; Agence National de la Recherche under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer; Canc?rop?le Ile-de-France; Chancellerie des universit?s de Paris (Legs Poix), Fondation pour la Recherche M?dicale; a donation by Elior; European Research Area Network on Cardiovascular Diseases (MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051), Institut National du Cancer; Inserm Program Heterogeneity of Tumors & Ecosystem; Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology; the Recherche Hospitalo-Universitaire Torino Lumi?re; the Seerave Foundation; the Site de Recherche int?gr?e sur le Cancer Stratified Oncology Cell DNA Repair and Tumor Immune Elimination; and Cancer Research and Personalized Medicine. Author contributions: J. Paillet performed the experiments with support from C. Plantureux, S. L?vesque, J. Le Naour, G. Stoll, P. Caudana, J. Tosello Boari, N. Bloy, S. Lachkar, I. Martins, A. Checcoli, G. Autret, B. Lekbaby, J. Augustin, Y. Kim, and J.G. Pol. P. Opolon and A. Sauvat performed anatomopathological analyses. A. Delaune, N. Robil, P. de la Grange, J. Hamroune, and F. Letourneur contributed to transcriptomic data analyses. P.S.C. Leung, M.E. Gershwin, J.S. Zhu, and M.J. Kurth produced 2OA-BSA. S. Gujar, C. Coulouarn, L. Fouassier, L. Zitvogel, E. Piaggio, C. Housset, P. Soussan, M. Chiara Maiuri provided critical input to the project and edited the manuscript. G. Kroemer and J.G. Pol conceived and directed the project. G. Kroemer and J.G. Pol wrote the manuscript with input by J. Paillet.

Publisher Copyright:
© 2021 Paillet et al.

ASJC Scopus Subject Areas

General Medicine

PubMed: MeSH publication types

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

ODD de l’ONU

Cette action contribue à la réalisation des objectifs de développement durable suivants

Accès au document

10.1084/jem.20200853

Autres fichiers et liens

Citer

Paillet, J., Plantureux, C., Lévesque, S., Le Naour, J., Stoll, G., Sauvat, A., Caudana, P., Boari, J. T., Bloy, N., Lachkar, S., Martins, I., Opolon, P., Checcoli, A., Delaune, A., Robil, N., de la Grange, P., Hamroune, J., Letourneur, F., Autret, G., ... Pol, J. G. (2021). Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma. Journal of Experimental Medicine, 218(10), Article e20200853. https://doi.org/10.1084/jem.20200853

Paillet, J, Plantureux, C, Lévesque, S, Le Naour, J, Stoll, G, Sauvat, A, Caudana, P, Boari, JT, Bloy, N, Lachkar, S, Martins, I, Opolon, P, Checcoli, A, Delaune, A, Robil, N, de la Grange, P, Hamroune, J, Letourneur, F, Autret, G, Leung, PSC, Gershwin, ME, Zhu, JS, Kurth, MJ, Lekbaby, B, Augustin, J, Kim, Y, Gujar, S, Coulouarn, C, Fouassier, L, Zitvogel, L, Piaggio, E, Housset, C, Soussan, P, Maiuri, MC, Kroemer, G & Pol, JG 2021, 'Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma', Journal of Experimental Medicine, vol. 218, n° 10, e20200853. https://doi.org/10.1084/jem.20200853

@article{3fa421a788ea4ab4b31ff73493209083,

title = "Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma",

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.",

author = "Juliette Paillet and C{\'e}leste Plantureux and Sarah L{\'e}vesque and {Le Naour}, Julie and Gautier Stoll and Allan Sauvat and Pamela Caudana and Boari, {Jimena Tosello} and Norma Bloy and Sylvie Lachkar and Isabelle Martins and Paule Opolon and Andrea Checcoli and Agathe Delaune and No{\'e}mie Robil and {de la Grange}, Pierre and Juliette Hamroune and Franck Letourneur and Gwennhael Autret and Leung, {Patrick S.C.} and Gershwin, {M. Eric} and Zhu, {Jie S.} and Kurth, {Mark J.} and Bouchra Lekbaby and J{\'e}r{\'e}my Augustin and Youra Kim and Shashi Gujar and C{\'e}dric Coulouarn and Laura Fouassier and Laurence Zitvogel and Eliane Piaggio and Chantal Housset and Patrick Soussan and Maiuri, {Maria Chiara} and Guido Kroemer and Pol, {Jonathan G.}",

note = "Funding Information: J. Paillet is supported by the Association pour la lutte contre les maladies inflammatoires du foie et des voies biliaires. S. Gujar is supported by Dalhousie Medical Research Foundation, Canadian Cancer Society, and Canadian Institutes of Health Research. J.G. Pol is supported by the Association Fran{\c c}aise d{\textquoteright}H{\'e}patologie; Site de Recherche int{\'e}gr{\'e}e sur le Cancer Cancer Research and Personalized Medicine; Seerave Foundation; Multi-Organism Institute (ITMO) Aviesan Cancer (National Alliance for Life Sciences and Health); and Institut National du Cancer. G. Kroemer is supported by the Ligue contre le Cancer ({\'e}quipe labellis{\'e}e); Agence National de la Recherche (ANR) – Projets blancs; Agence National de la Recherche under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer; Canc{\'e}rop{\^o}le Ile-de-France; Chancellerie des universit{\'e}s de Paris (Legs Poix), Fondation pour la Recherche M{\'e}dicale; a donation by Elior; European Research Area Network on Cardiovascular Diseases (MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project On-cobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051), Institut National du Cancer; Inserm Program Heterogeneity of Tumors & Ecosystem; Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology; the Recherche Hospitalo-Universitaire Torino Lumi{\`e}re; the Seerave Foundation; the Site de Recherche int{\'e}gr{\'e}e sur le Cancer Stratified Oncology Cell DNA Repair and Tumor Immune Elimination; and Cancer Research and Personalized Medicine. Funding Information: We would like to thank Estelle Dev?vre and H?l?ne Forher-Ting (Centre d?Histologie, d?Imagerie et de Cytom?trie core facility, Cordeliers Research Center, Institut National de la Sant? et de la Recherche M?dicale [INSERM] U1138, Paris) and the staff of the histo-cytopathology core facility of the Gustave Roussy cancer campus (Villejuif, France), as well as the staff of the Genom?IC platform of the Cochin Institute (INSERM U1016, Paris) for their assistance in flow cytometry, histology, and transcriptomic analyses, respectively. We also thank Pr. Raoul Poupon for having supported this project since the very beginning. J. Paillet is supported by the Association pour la lutte contre les maladies inflammatoires du foie et des voies biliaires. S. Gujar is supported by Dalhousie Medical Research Foundation, Canadian Cancer Society, and Canadian Institutes of Health Research. J.G. Pol is supported by the Association Fran?aise d?H?patologie; Site de Recherche int?gr?e sur le Cancer Cancer Research and Personalized Medicine; Seerave Foundation; Multi-Organism Institute (ITMO) Aviesan Cancer (National Alliance for Life Sciences and Health); and Institut National du Cancer. G. Kroemer is supported by the Ligue contre le Cancer (?quipe labellis?e); Agence National de la Recherche (ANR) ? Projets blancs; Agence National de la Recherche under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer; Canc?rop?le Ile-de-France; Chancellerie des universit?s de Paris (Legs Poix), Fondation pour la Recherche M?dicale; a donation by Elior; European Research Area Network on Cardiovascular Diseases (MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051), Institut National du Cancer; Inserm Program Heterogeneity of Tumors & Ecosystem; Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology; the Recherche Hospitalo-Universitaire Torino Lumi?re; the Seerave Foundation; the Site de Recherche int?gr?e sur le Cancer Stratified Oncology Cell DNA Repair and Tumor Immune Elimination; and Cancer Research and Personalized Medicine. Author contributions: J. Paillet performed the experiments with support from C. Plantureux, S. L?vesque, J. Le Naour, G. Stoll, P. Caudana, J. Tosello Boari, N. Bloy, S. Lachkar, I. Martins, A. Checcoli, G. Autret, B. Lekbaby, J. Augustin, Y. Kim, and J.G. Pol. P. Opolon and A. Sauvat performed anatomopathological analyses. A. Delaune, N. Robil, P. de la Grange, J. Hamroune, and F. Letourneur contributed to transcriptomic data analyses. P.S.C. Leung, M.E. Gershwin, J.S. Zhu, and M.J. Kurth produced 2OA-BSA. S. Gujar, C. Coulouarn, L. Fouassier, L. Zitvogel, E. Piaggio, C. Housset, P. Soussan, M. Chiara Maiuri provided critical input to the project and edited the manuscript. G. Kroemer and J.G. Pol conceived and directed the project. G. Kroemer and J.G. Pol wrote the manuscript with input by J. Paillet. Publisher Copyright: {\textcopyright} 2021 Paillet et al.",

year = "2021",

month = sep,

day = "8",

doi = "10.1084/jem.20200853",

language = "English",

volume = "218",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "10",

}

TY - JOUR

T1 - Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma

AU - Paillet, Juliette

AU - Plantureux, Céleste

AU - Lévesque, Sarah

AU - Le Naour, Julie

AU - Stoll, Gautier

AU - Sauvat, Allan

AU - Caudana, Pamela

AU - Boari, Jimena Tosello

AU - Bloy, Norma

AU - Lachkar, Sylvie

AU - Martins, Isabelle

AU - Opolon, Paule

AU - Checcoli, Andrea

AU - Delaune, Agathe

AU - Robil, Noémie

AU - de la Grange, Pierre

AU - Hamroune, Juliette

AU - Letourneur, Franck

AU - Autret, Gwennhael

AU - Leung, Patrick S.C.

AU - Gershwin, M. Eric

AU - Zhu, Jie S.

AU - Kurth, Mark J.

AU - Lekbaby, Bouchra

AU - Augustin, Jérémy

AU - Kim, Youra

AU - Gujar, Shashi

AU - Coulouarn, Cédric

AU - Fouassier, Laura

AU - Zitvogel, Laurence

AU - Piaggio, Eliane

AU - Housset, Chantal

AU - Soussan, Patrick

AU - Maiuri, Maria Chiara

AU - Kroemer, Guido

AU - Pol, Jonathan G.

N1 - Funding Information: J. Paillet is supported by the Association pour la lutte contre les maladies inflammatoires du foie et des voies biliaires. S. Gujar is supported by Dalhousie Medical Research Foundation, Canadian Cancer Society, and Canadian Institutes of Health Research. J.G. Pol is supported by the Association Française d’Hépatologie; Site de Recherche intégrée sur le Cancer Cancer Research and Personalized Medicine; Seerave Foundation; Multi-Organism Institute (ITMO) Aviesan Cancer (National Alliance for Life Sciences and Health); and Institut National du Cancer. G. Kroemer is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; Agence National de la Recherche under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer; Cancéropôle Ile-de-France; Chancellerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale; a donation by Elior; European Research Area Network on Cardiovascular Diseases (MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project On-cobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051), Institut National du Cancer; Inserm Program Heterogeneity of Tumors & Ecosystem; Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology; the Recherche Hospitalo-Universitaire Torino Lumière; the Seerave Foundation; the Site de Recherche intégrée sur le Cancer Stratified Oncology Cell DNA Repair and Tumor Immune Elimination; and Cancer Research and Personalized Medicine. Funding Information: We would like to thank Estelle Dev?vre and H?l?ne Forher-Ting (Centre d?Histologie, d?Imagerie et de Cytom?trie core facility, Cordeliers Research Center, Institut National de la Sant? et de la Recherche M?dicale [INSERM] U1138, Paris) and the staff of the histo-cytopathology core facility of the Gustave Roussy cancer campus (Villejuif, France), as well as the staff of the Genom?IC platform of the Cochin Institute (INSERM U1016, Paris) for their assistance in flow cytometry, histology, and transcriptomic analyses, respectively. We also thank Pr. Raoul Poupon for having supported this project since the very beginning. J. Paillet is supported by the Association pour la lutte contre les maladies inflammatoires du foie et des voies biliaires. S. Gujar is supported by Dalhousie Medical Research Foundation, Canadian Cancer Society, and Canadian Institutes of Health Research. J.G. Pol is supported by the Association Fran?aise d?H?patologie; Site de Recherche int?gr?e sur le Cancer Cancer Research and Personalized Medicine; Seerave Foundation; Multi-Organism Institute (ITMO) Aviesan Cancer (National Alliance for Life Sciences and Health); and Institut National du Cancer. G. Kroemer is supported by the Ligue contre le Cancer (?quipe labellis?e); Agence National de la Recherche (ANR) ? Projets blancs; Agence National de la Recherche under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer; Canc?rop?le Ile-de-France; Chancellerie des universit?s de Paris (Legs Poix), Fondation pour la Recherche M?dicale; a donation by Elior; European Research Area Network on Cardiovascular Diseases (MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051), Institut National du Cancer; Inserm Program Heterogeneity of Tumors & Ecosystem; Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology; the Recherche Hospitalo-Universitaire Torino Lumi?re; the Seerave Foundation; the Site de Recherche int?gr?e sur le Cancer Stratified Oncology Cell DNA Repair and Tumor Immune Elimination; and Cancer Research and Personalized Medicine. Author contributions: J. Paillet performed the experiments with support from C. Plantureux, S. L?vesque, J. Le Naour, G. Stoll, P. Caudana, J. Tosello Boari, N. Bloy, S. Lachkar, I. Martins, A. Checcoli, G. Autret, B. Lekbaby, J. Augustin, Y. Kim, and J.G. Pol. P. Opolon and A. Sauvat performed anatomopathological analyses. A. Delaune, N. Robil, P. de la Grange, J. Hamroune, and F. Letourneur contributed to transcriptomic data analyses. P.S.C. Leung, M.E. Gershwin, J.S. Zhu, and M.J. Kurth produced 2OA-BSA. S. Gujar, C. Coulouarn, L. Fouassier, L. Zitvogel, E. Piaggio, C. Housset, P. Soussan, M. Chiara Maiuri provided critical input to the project and edited the manuscript. G. Kroemer and J.G. Pol conceived and directed the project. G. Kroemer and J.G. Pol wrote the manuscript with input by J. Paillet. Publisher Copyright: © 2021 Paillet et al.

PY - 2021/9/8

Y1 - 2021/9/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85114778505&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85114778505&partnerID=8YFLogxK

U2 - 10.1084/jem.20200853

DO - 10.1084/jem.20200853

M3 - Article

C2 - 34495298

AN - SCOPUS:85114778505

SN - 0022-1007

VL - 218

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 10

M1 - e20200853

ER -

Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma

Résumé

Note bibliographique

ASJC Scopus Subject Areas

PubMed: MeSH publication types

ODD de l’ONU

Accès au document

Autres fichiers et liens

Empreinte numérique

Citer