A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers
Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but the mechanisms underlying their immunosuppressive effects remain unknown. By inducing the down-regulation of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in the ileum, post-A...
Gespeichert in:
| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2023-06, Vol.380 (6649) |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 6649 |
| container_start_page | |
| container_title | Science (American Association for the Advancement of Science) |
| container_volume | 380 |
| creator | Fidelle, Marine Rauber, Conrad Alves Costa Silva, Carolina Tian, Ai-Ling Lahmar, Imran de la Varende, Anne-Laure Mallard Zhao, Liwei Thelemaque, Cassandra Lebhar, Isabelle Messaoudene, Meriem Pizzato, Eugenie Birebent, Roxanne Mbogning Fonkou, Maxime Descartes Zoppi, Silvia Reni, Anna Dalban, Cécile Leduc, Marion Ferrere, Gladys Durand, Sylvère Ly, Pierre Silvin, Aymeric Mulder, Kevin Dutertre, Charles-Antoine Ginhoux, Florent Yonekura, Satoru Roberti, Maria Paula Tidjani-Alou, Maryam Terrisse, Safae Chen, Jianzhou Kepp, Oliver Schippers, Angela Wagner, Norbert Suárez-Gosálvez, Javier Kobold, Sebastian Fahrner, Jean-Eudes Richard, Corentin Bosq, Jacques Lordello, Leonardo Vitali, Giacomo Galleron, Nathalie Quinquis, Benoît Le Chatelier, Emmanuelle Blanchard, Lucas Girard, Jean-Philippe Jarry, Anne Gervois, Nadine Godefroy, Emmanuelle Labarrière, Nathalie Koschny, Ronald Daillère, Romain Besse, Benjamin Truntzer, Caroline Ghiringhelli, François Coatnoan, Nicolas Mhanna, Vanessa Klatzmann, David Drubay, Damien Albiges, Laurence Thomas, Andrew Maltez Segata, Nicola Danlos, François-Xavier Marabelle, Aurélien Routy, Bertrand Derosa, Lisa Kroemer, Guido Zitvogel, Laurence |
| description | Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but the mechanisms underlying their immunosuppressive effects remain unknown. By inducing the down-regulation of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in the ileum, post-ABX gut recolonization by Enterocloster species drove the emigration of enterotropic α4β7 + CD4 + regulatory T 17 cells into the tumor. These deleterious ABX effects were mimicked by oral gavage of Enterocloster species, by genetic deficiency, or by antibody-mediated neutralization of MAdCAM-1 and its receptor, α4β7 integrin. By contrast, fecal microbiota transplantation or interleukin-17A neutralization prevented ABX-induced immunosuppression. In independent lung, kidney, and bladder cancer patient cohorts, low serum levels of soluble MAdCAM-1 had a negative prognostic impact. Thus, the MAdCAM-1–α4β7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance. |
| doi_str_mv | 10.1126/science.abo2296 |
| format | Article |
| fullrecord | <record><control><sourceid>hal</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_inserm_04125703v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>oai_HAL_inserm_04125703v1</sourcerecordid><originalsourceid>FETCH-LOGICAL-h122t-b03c6473d04b813d7da98ddf962c1d86129308d1bcd895b6dc9d53969264a4273</originalsourceid><addsrcrecordid>eNotjkFLwzAYhoMobk7PXvMD7PyStGm-4xjqhIGXefJQ0nwZi7ZNSbqB_96Jnh54H3h5GLsXsBRC6sfsgh-cX9o2Son6gs0FYFWgBHXJ5gBKFwbqasZucv4EODtU12ymamnQIMzZx4r3waXYhjjZoo907OzkibuDd19jDMPEKSTvpsxD3x-HmI_jmHzO4eT52fo8hcF2fMed77r8O0Xu7Lkp5Vt2tbdd9nf_XLD356fdelNs315e16ttcRBSTkULyumyVgRla4Simiwaoj1q6QQZLSQqMCRaRwarVpNDqhRqlLq0pazVgj38_R5s14wp9DZ9N9GGZrPaNmHIPvUNlEJWNaiTUD_hiVyL</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers</title><source>Science Magazine</source><creator>Fidelle, Marine ; Rauber, Conrad ; Alves Costa Silva, Carolina ; Tian, Ai-Ling ; Lahmar, Imran ; de la Varende, Anne-Laure Mallard ; Zhao, Liwei ; Thelemaque, Cassandra ; Lebhar, Isabelle ; Messaoudene, Meriem ; Pizzato, Eugenie ; Birebent, Roxanne ; Mbogning Fonkou, Maxime Descartes ; Zoppi, Silvia ; Reni, Anna ; Dalban, Cécile ; Leduc, Marion ; Ferrere, Gladys ; Durand, Sylvère ; Ly, Pierre ; Silvin, Aymeric ; Mulder, Kevin ; Dutertre, Charles-Antoine ; Ginhoux, Florent ; Yonekura, Satoru ; Roberti, Maria Paula ; Tidjani-Alou, Maryam ; Terrisse, Safae ; Chen, Jianzhou ; Kepp, Oliver ; Schippers, Angela ; Wagner, Norbert ; Suárez-Gosálvez, Javier ; Kobold, Sebastian ; Fahrner, Jean-Eudes ; Richard, Corentin ; Bosq, Jacques ; Lordello, Leonardo ; Vitali, Giacomo ; Galleron, Nathalie ; Quinquis, Benoît ; Le Chatelier, Emmanuelle ; Blanchard, Lucas ; Girard, Jean-Philippe ; Jarry, Anne ; Gervois, Nadine ; Godefroy, Emmanuelle ; Labarrière, Nathalie ; Koschny, Ronald ; Daillère, Romain ; Besse, Benjamin ; Truntzer, Caroline ; Ghiringhelli, François ; Coatnoan, Nicolas ; Mhanna, Vanessa ; Klatzmann, David ; Drubay, Damien ; Albiges, Laurence ; Thomas, Andrew Maltez ; Segata, Nicola ; Danlos, François-Xavier ; Marabelle, Aurélien ; Routy, Bertrand ; Derosa, Lisa ; Kroemer, Guido ; Zitvogel, Laurence</creator><creatorcontrib>Fidelle, Marine ; Rauber, Conrad ; Alves Costa Silva, Carolina ; Tian, Ai-Ling ; Lahmar, Imran ; de la Varende, Anne-Laure Mallard ; Zhao, Liwei ; Thelemaque, Cassandra ; Lebhar, Isabelle ; Messaoudene, Meriem ; Pizzato, Eugenie ; Birebent, Roxanne ; Mbogning Fonkou, Maxime Descartes ; Zoppi, Silvia ; Reni, Anna ; Dalban, Cécile ; Leduc, Marion ; Ferrere, Gladys ; Durand, Sylvère ; Ly, Pierre ; Silvin, Aymeric ; Mulder, Kevin ; Dutertre, Charles-Antoine ; Ginhoux, Florent ; Yonekura, Satoru ; Roberti, Maria Paula ; Tidjani-Alou, Maryam ; Terrisse, Safae ; Chen, Jianzhou ; Kepp, Oliver ; Schippers, Angela ; Wagner, Norbert ; Suárez-Gosálvez, Javier ; Kobold, Sebastian ; Fahrner, Jean-Eudes ; Richard, Corentin ; Bosq, Jacques ; Lordello, Leonardo ; Vitali, Giacomo ; Galleron, Nathalie ; Quinquis, Benoît ; Le Chatelier, Emmanuelle ; Blanchard, Lucas ; Girard, Jean-Philippe ; Jarry, Anne ; Gervois, Nadine ; Godefroy, Emmanuelle ; Labarrière, Nathalie ; Koschny, Ronald ; Daillère, Romain ; Besse, Benjamin ; Truntzer, Caroline ; Ghiringhelli, François ; Coatnoan, Nicolas ; Mhanna, Vanessa ; Klatzmann, David ; Drubay, Damien ; Albiges, Laurence ; Thomas, Andrew Maltez ; Segata, Nicola ; Danlos, François-Xavier ; Marabelle, Aurélien ; Routy, Bertrand ; Derosa, Lisa ; Kroemer, Guido ; Zitvogel, Laurence</creatorcontrib><description>Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but the mechanisms underlying their immunosuppressive effects remain unknown. By inducing the down-regulation of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in the ileum, post-ABX gut recolonization by Enterocloster species drove the emigration of enterotropic α4β7 + CD4 + regulatory T 17 cells into the tumor. These deleterious ABX effects were mimicked by oral gavage of Enterocloster species, by genetic deficiency, or by antibody-mediated neutralization of MAdCAM-1 and its receptor, α4β7 integrin. By contrast, fecal microbiota transplantation or interleukin-17A neutralization prevented ABX-induced immunosuppression. In independent lung, kidney, and bladder cancer patient cohorts, low serum levels of soluble MAdCAM-1 had a negative prognostic impact. Thus, the MAdCAM-1–α4β7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.abo2296</identifier><identifier>PMID: 37289890</identifier><language>eng</language><publisher>American Association for the Advancement of Science (AAAS)</publisher><subject>Life Sciences</subject><ispartof>Science (American Association for the Advancement of Science), 2023-06, Vol.380 (6649)</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-7808-8394 ; 0000-0001-7950-3652 ; 0000-0002-4981-6639 ; 0000-0002-1583-5794 ; 0000-0002-8357-1073 ; 0000-0003-0429-3712 ; 0000-0003-1880-064X ; 0000-0001-5090-8189 ; 0000-0002-2724-0536 ; 0000-0003-0895-4813 ; 0000-0002-0054-3422 ; 0000-0003-3467-2991 ; 0000-0002-3645-3904 ; 0000-0002-5612-4673 ; 0000-0002-5734-3480 ; 0000-0002-2156-8426 ; 0000-0002-9334-4405 ; 0000-0002-9154-1691 ; 0000-0003-0527-2964 ; 0000-0002-5816-3019 ; 0000-0003-1920-142X ; 0000-0001-5581-3891 ; 0000-0002-4623-780X ; 0000-0003-4019-9555 ; 0000-0002-3489-7800 ; 0000-0003-2748-8555 ; 0000-0001-6103-9185 ; 0000-0002-0167-6235 ; 0000-0003-3617-6377 ; 0000-0003-1596-0998 ; 0000-0002-1568-6581 ; 0000-0001-5788-6840 ; 0000-0002-6081-9558 ; 0000-0001-6581-8418 ; 0000-0002-1407-6546 ; 0000-0001-8460-6445 ; 0000-0002-5589-9688 ; 0000-0002-7573-969X ; 0000-0002-2857-7755 ; 0000-0002-0092-3919 ; 0000-0003-2132-7486 ; 0000-0001-6942-7086 ; 0000-0003-4047-3016 ; 0000-0001-5789-3354</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://inserm.hal.science/inserm-04125703$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Fidelle, Marine</creatorcontrib><creatorcontrib>Rauber, Conrad</creatorcontrib><creatorcontrib>Alves Costa Silva, Carolina</creatorcontrib><creatorcontrib>Tian, Ai-Ling</creatorcontrib><creatorcontrib>Lahmar, Imran</creatorcontrib><creatorcontrib>de la Varende, Anne-Laure Mallard</creatorcontrib><creatorcontrib>Zhao, Liwei</creatorcontrib><creatorcontrib>Thelemaque, Cassandra</creatorcontrib><creatorcontrib>Lebhar, Isabelle</creatorcontrib><creatorcontrib>Messaoudene, Meriem</creatorcontrib><creatorcontrib>Pizzato, Eugenie</creatorcontrib><creatorcontrib>Birebent, Roxanne</creatorcontrib><creatorcontrib>Mbogning Fonkou, Maxime Descartes</creatorcontrib><creatorcontrib>Zoppi, Silvia</creatorcontrib><creatorcontrib>Reni, Anna</creatorcontrib><creatorcontrib>Dalban, Cécile</creatorcontrib><creatorcontrib>Leduc, Marion</creatorcontrib><creatorcontrib>Ferrere, Gladys</creatorcontrib><creatorcontrib>Durand, Sylvère</creatorcontrib><creatorcontrib>Ly, Pierre</creatorcontrib><creatorcontrib>Silvin, Aymeric</creatorcontrib><creatorcontrib>Mulder, Kevin</creatorcontrib><creatorcontrib>Dutertre, Charles-Antoine</creatorcontrib><creatorcontrib>Ginhoux, Florent</creatorcontrib><creatorcontrib>Yonekura, Satoru</creatorcontrib><creatorcontrib>Roberti, Maria Paula</creatorcontrib><creatorcontrib>Tidjani-Alou, Maryam</creatorcontrib><creatorcontrib>Terrisse, Safae</creatorcontrib><creatorcontrib>Chen, Jianzhou</creatorcontrib><creatorcontrib>Kepp, Oliver</creatorcontrib><creatorcontrib>Schippers, Angela</creatorcontrib><creatorcontrib>Wagner, Norbert</creatorcontrib><creatorcontrib>Suárez-Gosálvez, Javier</creatorcontrib><creatorcontrib>Kobold, Sebastian</creatorcontrib><creatorcontrib>Fahrner, Jean-Eudes</creatorcontrib><creatorcontrib>Richard, Corentin</creatorcontrib><creatorcontrib>Bosq, Jacques</creatorcontrib><creatorcontrib>Lordello, Leonardo</creatorcontrib><creatorcontrib>Vitali, Giacomo</creatorcontrib><creatorcontrib>Galleron, Nathalie</creatorcontrib><creatorcontrib>Quinquis, Benoît</creatorcontrib><creatorcontrib>Le Chatelier, Emmanuelle</creatorcontrib><creatorcontrib>Blanchard, Lucas</creatorcontrib><creatorcontrib>Girard, Jean-Philippe</creatorcontrib><creatorcontrib>Jarry, Anne</creatorcontrib><creatorcontrib>Gervois, Nadine</creatorcontrib><creatorcontrib>Godefroy, Emmanuelle</creatorcontrib><creatorcontrib>Labarrière, Nathalie</creatorcontrib><creatorcontrib>Koschny, Ronald</creatorcontrib><creatorcontrib>Daillère, Romain</creatorcontrib><creatorcontrib>Besse, Benjamin</creatorcontrib><creatorcontrib>Truntzer, Caroline</creatorcontrib><creatorcontrib>Ghiringhelli, François</creatorcontrib><creatorcontrib>Coatnoan, Nicolas</creatorcontrib><creatorcontrib>Mhanna, Vanessa</creatorcontrib><creatorcontrib>Klatzmann, David</creatorcontrib><creatorcontrib>Drubay, Damien</creatorcontrib><creatorcontrib>Albiges, Laurence</creatorcontrib><creatorcontrib>Thomas, Andrew Maltez</creatorcontrib><creatorcontrib>Segata, Nicola</creatorcontrib><creatorcontrib>Danlos, François-Xavier</creatorcontrib><creatorcontrib>Marabelle, Aurélien</creatorcontrib><creatorcontrib>Routy, Bertrand</creatorcontrib><creatorcontrib>Derosa, Lisa</creatorcontrib><creatorcontrib>Kroemer, Guido</creatorcontrib><creatorcontrib>Zitvogel, Laurence</creatorcontrib><title>A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers</title><title>Science (American Association for the Advancement of Science)</title><description>Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but the mechanisms underlying their immunosuppressive effects remain unknown. By inducing the down-regulation of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in the ileum, post-ABX gut recolonization by Enterocloster species drove the emigration of enterotropic α4β7 + CD4 + regulatory T 17 cells into the tumor. These deleterious ABX effects were mimicked by oral gavage of Enterocloster species, by genetic deficiency, or by antibody-mediated neutralization of MAdCAM-1 and its receptor, α4β7 integrin. By contrast, fecal microbiota transplantation or interleukin-17A neutralization prevented ABX-induced immunosuppression. In independent lung, kidney, and bladder cancer patient cohorts, low serum levels of soluble MAdCAM-1 had a negative prognostic impact. Thus, the MAdCAM-1–α4β7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.</description><subject>Life Sciences</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNotjkFLwzAYhoMobk7PXvMD7PyStGm-4xjqhIGXefJQ0nwZi7ZNSbqB_96Jnh54H3h5GLsXsBRC6sfsgh-cX9o2Son6gs0FYFWgBHXJ5gBKFwbqasZucv4EODtU12ymamnQIMzZx4r3waXYhjjZoo907OzkibuDd19jDMPEKSTvpsxD3x-HmI_jmHzO4eT52fo8hcF2fMed77r8O0Xu7Lkp5Vt2tbdd9nf_XLD356fdelNs315e16ttcRBSTkULyumyVgRla4Simiwaoj1q6QQZLSQqMCRaRwarVpNDqhRqlLq0pazVgj38_R5s14wp9DZ9N9GGZrPaNmHIPvUNlEJWNaiTUD_hiVyL</recordid><startdate>20230609</startdate><enddate>20230609</enddate><creator>Fidelle, Marine</creator><creator>Rauber, Conrad</creator><creator>Alves Costa Silva, Carolina</creator><creator>Tian, Ai-Ling</creator><creator>Lahmar, Imran</creator><creator>de la Varende, Anne-Laure Mallard</creator><creator>Zhao, Liwei</creator><creator>Thelemaque, Cassandra</creator><creator>Lebhar, Isabelle</creator><creator>Messaoudene, Meriem</creator><creator>Pizzato, Eugenie</creator><creator>Birebent, Roxanne</creator><creator>Mbogning Fonkou, Maxime Descartes</creator><creator>Zoppi, Silvia</creator><creator>Reni, Anna</creator><creator>Dalban, Cécile</creator><creator>Leduc, Marion</creator><creator>Ferrere, Gladys</creator><creator>Durand, Sylvère</creator><creator>Ly, Pierre</creator><creator>Silvin, Aymeric</creator><creator>Mulder, Kevin</creator><creator>Dutertre, Charles-Antoine</creator><creator>Ginhoux, Florent</creator><creator>Yonekura, Satoru</creator><creator>Roberti, Maria Paula</creator><creator>Tidjani-Alou, Maryam</creator><creator>Terrisse, Safae</creator><creator>Chen, Jianzhou</creator><creator>Kepp, Oliver</creator><creator>Schippers, Angela</creator><creator>Wagner, Norbert</creator><creator>Suárez-Gosálvez, Javier</creator><creator>Kobold, Sebastian</creator><creator>Fahrner, Jean-Eudes</creator><creator>Richard, Corentin</creator><creator>Bosq, Jacques</creator><creator>Lordello, Leonardo</creator><creator>Vitali, Giacomo</creator><creator>Galleron, Nathalie</creator><creator>Quinquis, Benoît</creator><creator>Le Chatelier, Emmanuelle</creator><creator>Blanchard, Lucas</creator><creator>Girard, Jean-Philippe</creator><creator>Jarry, Anne</creator><creator>Gervois, Nadine</creator><creator>Godefroy, Emmanuelle</creator><creator>Labarrière, Nathalie</creator><creator>Koschny, Ronald</creator><creator>Daillère, Romain</creator><creator>Besse, Benjamin</creator><creator>Truntzer, Caroline</creator><creator>Ghiringhelli, François</creator><creator>Coatnoan, Nicolas</creator><creator>Mhanna, Vanessa</creator><creator>Klatzmann, David</creator><creator>Drubay, Damien</creator><creator>Albiges, Laurence</creator><creator>Thomas, Andrew Maltez</creator><creator>Segata, Nicola</creator><creator>Danlos, François-Xavier</creator><creator>Marabelle, Aurélien</creator><creator>Routy, Bertrand</creator><creator>Derosa, Lisa</creator><creator>Kroemer, Guido</creator><creator>Zitvogel, Laurence</creator><general>American Association for the Advancement of Science (AAAS)</general><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0002-7808-8394</orcidid><orcidid>https://orcid.org/0000-0001-7950-3652</orcidid><orcidid>https://orcid.org/0000-0002-4981-6639</orcidid><orcidid>https://orcid.org/0000-0002-1583-5794</orcidid><orcidid>https://orcid.org/0000-0002-8357-1073</orcidid><orcidid>https://orcid.org/0000-0003-0429-3712</orcidid><orcidid>https://orcid.org/0000-0003-1880-064X</orcidid><orcidid>https://orcid.org/0000-0001-5090-8189</orcidid><orcidid>https://orcid.org/0000-0002-2724-0536</orcidid><orcidid>https://orcid.org/0000-0003-0895-4813</orcidid><orcidid>https://orcid.org/0000-0002-0054-3422</orcidid><orcidid>https://orcid.org/0000-0003-3467-2991</orcidid><orcidid>https://orcid.org/0000-0002-3645-3904</orcidid><orcidid>https://orcid.org/0000-0002-5612-4673</orcidid><orcidid>https://orcid.org/0000-0002-5734-3480</orcidid><orcidid>https://orcid.org/0000-0002-2156-8426</orcidid><orcidid>https://orcid.org/0000-0002-9334-4405</orcidid><orcidid>https://orcid.org/0000-0002-9154-1691</orcidid><orcidid>https://orcid.org/0000-0003-0527-2964</orcidid><orcidid>https://orcid.org/0000-0002-5816-3019</orcidid><orcidid>https://orcid.org/0000-0003-1920-142X</orcidid><orcidid>https://orcid.org/0000-0001-5581-3891</orcidid><orcidid>https://orcid.org/0000-0002-4623-780X</orcidid><orcidid>https://orcid.org/0000-0003-4019-9555</orcidid><orcidid>https://orcid.org/0000-0002-3489-7800</orcidid><orcidid>https://orcid.org/0000-0003-2748-8555</orcidid><orcidid>https://orcid.org/0000-0001-6103-9185</orcidid><orcidid>https://orcid.org/0000-0002-0167-6235</orcidid><orcidid>https://orcid.org/0000-0003-3617-6377</orcidid><orcidid>https://orcid.org/0000-0003-1596-0998</orcidid><orcidid>https://orcid.org/0000-0002-1568-6581</orcidid><orcidid>https://orcid.org/0000-0001-5788-6840</orcidid><orcidid>https://orcid.org/0000-0002-6081-9558</orcidid><orcidid>https://orcid.org/0000-0001-6581-8418</orcidid><orcidid>https://orcid.org/0000-0002-1407-6546</orcidid><orcidid>https://orcid.org/0000-0001-8460-6445</orcidid><orcidid>https://orcid.org/0000-0002-5589-9688</orcidid><orcidid>https://orcid.org/0000-0002-7573-969X</orcidid><orcidid>https://orcid.org/0000-0002-2857-7755</orcidid><orcidid>https://orcid.org/0000-0002-0092-3919</orcidid><orcidid>https://orcid.org/0000-0003-2132-7486</orcidid><orcidid>https://orcid.org/0000-0001-6942-7086</orcidid><orcidid>https://orcid.org/0000-0003-4047-3016</orcidid><orcidid>https://orcid.org/0000-0001-5789-3354</orcidid></search><sort><creationdate>20230609</creationdate><title>A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers</title><author>Fidelle, Marine ; Rauber, Conrad ; Alves Costa Silva, Carolina ; Tian, Ai-Ling ; Lahmar, Imran ; de la Varende, Anne-Laure Mallard ; Zhao, Liwei ; Thelemaque, Cassandra ; Lebhar, Isabelle ; Messaoudene, Meriem ; Pizzato, Eugenie ; Birebent, Roxanne ; Mbogning Fonkou, Maxime Descartes ; Zoppi, Silvia ; Reni, Anna ; Dalban, Cécile ; Leduc, Marion ; Ferrere, Gladys ; Durand, Sylvère ; Ly, Pierre ; Silvin, Aymeric ; Mulder, Kevin ; Dutertre, Charles-Antoine ; Ginhoux, Florent ; Yonekura, Satoru ; Roberti, Maria Paula ; Tidjani-Alou, Maryam ; Terrisse, Safae ; Chen, Jianzhou ; Kepp, Oliver ; Schippers, Angela ; Wagner, Norbert ; Suárez-Gosálvez, Javier ; Kobold, Sebastian ; Fahrner, Jean-Eudes ; Richard, Corentin ; Bosq, Jacques ; Lordello, Leonardo ; Vitali, Giacomo ; Galleron, Nathalie ; Quinquis, Benoît ; Le Chatelier, Emmanuelle ; Blanchard, Lucas ; Girard, Jean-Philippe ; Jarry, Anne ; Gervois, Nadine ; Godefroy, Emmanuelle ; Labarrière, Nathalie ; Koschny, Ronald ; Daillère, Romain ; Besse, Benjamin ; Truntzer, Caroline ; Ghiringhelli, François ; Coatnoan, Nicolas ; Mhanna, Vanessa ; Klatzmann, David ; Drubay, Damien ; Albiges, Laurence ; Thomas, Andrew Maltez ; Segata, Nicola ; Danlos, François-Xavier ; Marabelle, Aurélien ; Routy, Bertrand ; Derosa, Lisa ; Kroemer, Guido ; Zitvogel, Laurence</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h122t-b03c6473d04b813d7da98ddf962c1d86129308d1bcd895b6dc9d53969264a4273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Life Sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fidelle, Marine</creatorcontrib><creatorcontrib>Rauber, Conrad</creatorcontrib><creatorcontrib>Alves Costa Silva, Carolina</creatorcontrib><creatorcontrib>Tian, Ai-Ling</creatorcontrib><creatorcontrib>Lahmar, Imran</creatorcontrib><creatorcontrib>de la Varende, Anne-Laure Mallard</creatorcontrib><creatorcontrib>Zhao, Liwei</creatorcontrib><creatorcontrib>Thelemaque, Cassandra</creatorcontrib><creatorcontrib>Lebhar, Isabelle</creatorcontrib><creatorcontrib>Messaoudene, Meriem</creatorcontrib><creatorcontrib>Pizzato, Eugenie</creatorcontrib><creatorcontrib>Birebent, Roxanne</creatorcontrib><creatorcontrib>Mbogning Fonkou, Maxime Descartes</creatorcontrib><creatorcontrib>Zoppi, Silvia</creatorcontrib><creatorcontrib>Reni, Anna</creatorcontrib><creatorcontrib>Dalban, Cécile</creatorcontrib><creatorcontrib>Leduc, Marion</creatorcontrib><creatorcontrib>Ferrere, Gladys</creatorcontrib><creatorcontrib>Durand, Sylvère</creatorcontrib><creatorcontrib>Ly, Pierre</creatorcontrib><creatorcontrib>Silvin, Aymeric</creatorcontrib><creatorcontrib>Mulder, Kevin</creatorcontrib><creatorcontrib>Dutertre, Charles-Antoine</creatorcontrib><creatorcontrib>Ginhoux, Florent</creatorcontrib><creatorcontrib>Yonekura, Satoru</creatorcontrib><creatorcontrib>Roberti, Maria Paula</creatorcontrib><creatorcontrib>Tidjani-Alou, Maryam</creatorcontrib><creatorcontrib>Terrisse, Safae</creatorcontrib><creatorcontrib>Chen, Jianzhou</creatorcontrib><creatorcontrib>Kepp, Oliver</creatorcontrib><creatorcontrib>Schippers, Angela</creatorcontrib><creatorcontrib>Wagner, Norbert</creatorcontrib><creatorcontrib>Suárez-Gosálvez, Javier</creatorcontrib><creatorcontrib>Kobold, Sebastian</creatorcontrib><creatorcontrib>Fahrner, Jean-Eudes</creatorcontrib><creatorcontrib>Richard, Corentin</creatorcontrib><creatorcontrib>Bosq, Jacques</creatorcontrib><creatorcontrib>Lordello, Leonardo</creatorcontrib><creatorcontrib>Vitali, Giacomo</creatorcontrib><creatorcontrib>Galleron, Nathalie</creatorcontrib><creatorcontrib>Quinquis, Benoît</creatorcontrib><creatorcontrib>Le Chatelier, Emmanuelle</creatorcontrib><creatorcontrib>Blanchard, Lucas</creatorcontrib><creatorcontrib>Girard, Jean-Philippe</creatorcontrib><creatorcontrib>Jarry, Anne</creatorcontrib><creatorcontrib>Gervois, Nadine</creatorcontrib><creatorcontrib>Godefroy, Emmanuelle</creatorcontrib><creatorcontrib>Labarrière, Nathalie</creatorcontrib><creatorcontrib>Koschny, Ronald</creatorcontrib><creatorcontrib>Daillère, Romain</creatorcontrib><creatorcontrib>Besse, Benjamin</creatorcontrib><creatorcontrib>Truntzer, Caroline</creatorcontrib><creatorcontrib>Ghiringhelli, François</creatorcontrib><creatorcontrib>Coatnoan, Nicolas</creatorcontrib><creatorcontrib>Mhanna, Vanessa</creatorcontrib><creatorcontrib>Klatzmann, David</creatorcontrib><creatorcontrib>Drubay, Damien</creatorcontrib><creatorcontrib>Albiges, Laurence</creatorcontrib><creatorcontrib>Thomas, Andrew Maltez</creatorcontrib><creatorcontrib>Segata, Nicola</creatorcontrib><creatorcontrib>Danlos, François-Xavier</creatorcontrib><creatorcontrib>Marabelle, Aurélien</creatorcontrib><creatorcontrib>Routy, Bertrand</creatorcontrib><creatorcontrib>Derosa, Lisa</creatorcontrib><creatorcontrib>Kroemer, Guido</creatorcontrib><creatorcontrib>Zitvogel, Laurence</creatorcontrib><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fidelle, Marine</au><au>Rauber, Conrad</au><au>Alves Costa Silva, Carolina</au><au>Tian, Ai-Ling</au><au>Lahmar, Imran</au><au>de la Varende, Anne-Laure Mallard</au><au>Zhao, Liwei</au><au>Thelemaque, Cassandra</au><au>Lebhar, Isabelle</au><au>Messaoudene, Meriem</au><au>Pizzato, Eugenie</au><au>Birebent, Roxanne</au><au>Mbogning Fonkou, Maxime Descartes</au><au>Zoppi, Silvia</au><au>Reni, Anna</au><au>Dalban, Cécile</au><au>Leduc, Marion</au><au>Ferrere, Gladys</au><au>Durand, Sylvère</au><au>Ly, Pierre</au><au>Silvin, Aymeric</au><au>Mulder, Kevin</au><au>Dutertre, Charles-Antoine</au><au>Ginhoux, Florent</au><au>Yonekura, Satoru</au><au>Roberti, Maria Paula</au><au>Tidjani-Alou, Maryam</au><au>Terrisse, Safae</au><au>Chen, Jianzhou</au><au>Kepp, Oliver</au><au>Schippers, Angela</au><au>Wagner, Norbert</au><au>Suárez-Gosálvez, Javier</au><au>Kobold, Sebastian</au><au>Fahrner, Jean-Eudes</au><au>Richard, Corentin</au><au>Bosq, Jacques</au><au>Lordello, Leonardo</au><au>Vitali, Giacomo</au><au>Galleron, Nathalie</au><au>Quinquis, Benoît</au><au>Le Chatelier, Emmanuelle</au><au>Blanchard, Lucas</au><au>Girard, Jean-Philippe</au><au>Jarry, Anne</au><au>Gervois, Nadine</au><au>Godefroy, Emmanuelle</au><au>Labarrière, Nathalie</au><au>Koschny, Ronald</au><au>Daillère, Romain</au><au>Besse, Benjamin</au><au>Truntzer, Caroline</au><au>Ghiringhelli, François</au><au>Coatnoan, Nicolas</au><au>Mhanna, Vanessa</au><au>Klatzmann, David</au><au>Drubay, Damien</au><au>Albiges, Laurence</au><au>Thomas, Andrew Maltez</au><au>Segata, Nicola</au><au>Danlos, François-Xavier</au><au>Marabelle, Aurélien</au><au>Routy, Bertrand</au><au>Derosa, Lisa</au><au>Kroemer, Guido</au><au>Zitvogel, Laurence</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><date>2023-06-09</date><risdate>2023</risdate><volume>380</volume><issue>6649</issue><issn>0036-8075</issn><eissn>1095-9203</eissn><abstract>Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but the mechanisms underlying their immunosuppressive effects remain unknown. By inducing the down-regulation of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in the ileum, post-ABX gut recolonization by Enterocloster species drove the emigration of enterotropic α4β7 + CD4 + regulatory T 17 cells into the tumor. These deleterious ABX effects were mimicked by oral gavage of Enterocloster species, by genetic deficiency, or by antibody-mediated neutralization of MAdCAM-1 and its receptor, α4β7 integrin. By contrast, fecal microbiota transplantation or interleukin-17A neutralization prevented ABX-induced immunosuppression. In independent lung, kidney, and bladder cancer patient cohorts, low serum levels of soluble MAdCAM-1 had a negative prognostic impact. Thus, the MAdCAM-1–α4β7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.</abstract><pub>American Association for the Advancement of Science (AAAS)</pub><pmid>37289890</pmid><doi>10.1126/science.abo2296</doi><orcidid>https://orcid.org/0000-0002-7808-8394</orcidid><orcidid>https://orcid.org/0000-0001-7950-3652</orcidid><orcidid>https://orcid.org/0000-0002-4981-6639</orcidid><orcidid>https://orcid.org/0000-0002-1583-5794</orcidid><orcidid>https://orcid.org/0000-0002-8357-1073</orcidid><orcidid>https://orcid.org/0000-0003-0429-3712</orcidid><orcidid>https://orcid.org/0000-0003-1880-064X</orcidid><orcidid>https://orcid.org/0000-0001-5090-8189</orcidid><orcidid>https://orcid.org/0000-0002-2724-0536</orcidid><orcidid>https://orcid.org/0000-0003-0895-4813</orcidid><orcidid>https://orcid.org/0000-0002-0054-3422</orcidid><orcidid>https://orcid.org/0000-0003-3467-2991</orcidid><orcidid>https://orcid.org/0000-0002-3645-3904</orcidid><orcidid>https://orcid.org/0000-0002-5612-4673</orcidid><orcidid>https://orcid.org/0000-0002-5734-3480</orcidid><orcidid>https://orcid.org/0000-0002-2156-8426</orcidid><orcidid>https://orcid.org/0000-0002-9334-4405</orcidid><orcidid>https://orcid.org/0000-0002-9154-1691</orcidid><orcidid>https://orcid.org/0000-0003-0527-2964</orcidid><orcidid>https://orcid.org/0000-0002-5816-3019</orcidid><orcidid>https://orcid.org/0000-0003-1920-142X</orcidid><orcidid>https://orcid.org/0000-0001-5581-3891</orcidid><orcidid>https://orcid.org/0000-0002-4623-780X</orcidid><orcidid>https://orcid.org/0000-0003-4019-9555</orcidid><orcidid>https://orcid.org/0000-0002-3489-7800</orcidid><orcidid>https://orcid.org/0000-0003-2748-8555</orcidid><orcidid>https://orcid.org/0000-0001-6103-9185</orcidid><orcidid>https://orcid.org/0000-0002-0167-6235</orcidid><orcidid>https://orcid.org/0000-0003-3617-6377</orcidid><orcidid>https://orcid.org/0000-0003-1596-0998</orcidid><orcidid>https://orcid.org/0000-0002-1568-6581</orcidid><orcidid>https://orcid.org/0000-0001-5788-6840</orcidid><orcidid>https://orcid.org/0000-0002-6081-9558</orcidid><orcidid>https://orcid.org/0000-0001-6581-8418</orcidid><orcidid>https://orcid.org/0000-0002-1407-6546</orcidid><orcidid>https://orcid.org/0000-0001-8460-6445</orcidid><orcidid>https://orcid.org/0000-0002-5589-9688</orcidid><orcidid>https://orcid.org/0000-0002-7573-969X</orcidid><orcidid>https://orcid.org/0000-0002-2857-7755</orcidid><orcidid>https://orcid.org/0000-0002-0092-3919</orcidid><orcidid>https://orcid.org/0000-0003-2132-7486</orcidid><orcidid>https://orcid.org/0000-0001-6942-7086</orcidid><orcidid>https://orcid.org/0000-0003-4047-3016</orcidid><orcidid>https://orcid.org/0000-0001-5789-3354</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2023-06, Vol.380 (6649) |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_inserm_04125703v1 |
| source | Science Magazine |
| subjects | Life Sciences |
| title | A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T17%3A38%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-hal&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20microbiota-modulated%20checkpoint%20directs%20immunosuppressive%20intestinal%20T%20cells%20into%20cancers&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Fidelle,%20Marine&rft.date=2023-06-09&rft.volume=380&rft.issue=6649&rft.issn=0036-8075&rft.eissn=1095-9203&rft_id=info:doi/10.1126/science.abo2296&rft_dat=%3Chal%3Eoai_HAL_inserm_04125703v1%3C/hal%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/37289890&rfr_iscdi=true |