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Antibodies against endogenous retroviruses promote lung cancer immunotherapy

免疫疗法 癌症研究 生发中心 抗体 免疫学 腺癌 肺癌 生物 癌症 免疫系统 B细胞 医学 病理 遗传学
作者
Kevin W. Ng,Jesse Boumelha,Katey S.S. Enfield,Jorge Almagro,Hongui Cha,Oriol Pich,Takahiro Karasaki,David A. Moore,Roberto Salgado,Monica Sivakumar,George R. Young,Míriam Molina‐Arcas,Sophie de Carné Trécesson,Panayiotis Anastasiou,Annika Fendler,Lewis Au,Scott T.C. Shepherd,Carlos Martínez-Ruiz,Clare Puttick,James R. Black,Thomas B.K. Watkins,Hye Min Kim,Seohee Shim,Nikhil Faulkner,Jan Attig,Selvaraju Veeriah,Neil Magno,Sophia Ward,Alexander M. Frankell,Maise Al Bakir,Emilia L. Lim,Mark S. Hill,Gareth A. Wilson,Daniel E. Cook,Nicolai J. Birkbak,Axel Behrens,Nadia Yousaf,Sanjay Popat,Allan Hackshaw,Andrew Rowan,Ariana Huebner,Brittany Campbell,Chris Bailey,Claudia Lee,Dhruva Biswas,Emma Colliver,Foteini Athanasopoulou,Hao‐Ran Zhai,Jayant K. Rane,Kristiana Grigoriadis,Michelle Dietzen,Michelle Leung,Mihaela Angelova,Olivia Lucas,Othman Al‐Sawaf,Rachel Rosenthal,Jérôme Nicod,Abigail Bunkum,Antonia Toncheva,Christopher Abbosh,Corentin Richard,Cristina Naceur‐Lombardelli,Francisco Gimeno-Valiente,Jie Min Lam,Kerstin Thol,Krupa Thakkar,Mariana Werner Sunderland,Martin Förster,Nnennaya Kanu,Paulina Prymas,Robert Bentham,Sadegh Saghafinia,Sergio A. Quezada,Sharon Vanloo,Simone Zaccaria,Siow Ming Lee,Sonya Hessey,Wing Kin Liu,Dionysis Papadatos-Pastos,James M. Wilson,Sarah Benafif,Tanya Ahmad,Elaine Borg,Mary Falzon,Reena Khiroya,Teresa Marafioti,Abigail Sharp,Camilla Pilotti,Harjot Kaur Dhanda,Kitty S. Chan,Nicole Gower,Rachel Leslie,Sean Smith,Andrew G. Nicholson,Eric Lim,Javier Herrero,Carla Castignani,Elizabeth Larose Cadieux,Jonas Demeulemeester,Peter Van Loo,Karl S. Peggs,Catarina Veiga,Gary Royle,Charles-Antoine Collins-Fekete,Alexander James Procter,Arjun Nair,Asia Ahmed,Magali Taylor,Neal Navani,Ricky M. Thakrar,David Lawrence,Davide Patrini,Emma Nye,Richard Stone,David Chuter,Mairead MacKenzie,Francesco Fraioli,Paul Ashford,Sam M. Janes,Miljana Tanić,Stephan Beck,Alexandra Rice,Anand Devaraj,Chiara Proli,Daniel Kaniu,Harshil Bhayani,Hema Chavan,Hilgardt Raubenheimer,Lyn Ambrose,Mpho Malima,Nadia Fernandes,Paulo De Sousa,Pratibha Shah,Sarah Booth,Silviu Buderi,Simon Jordan,Sofina Begum,Ekaterini Boleti,Grant D. Stewart,Alastair Magness,Clare E. Weeden,Dina Levi,Eva Grönroos,Jacki Goldman,Mickael Escudero,Philip Hobson,Roberto Vendramin,Stefan Boeing,Tamara Denner,Vittorio Barbè,Wei-Ting Lu,William Hill,Yutaka Naito,Zoe Ramsden,Anca Grapa,Hanyun Zhang,Khalid AbdulJabbar,Xiaoxi Pan,Kayleigh Gilbert,Angeliki Karamani,Benny Chain,David R. Pearce,Despoina Karagianni,Elena Hoxha,Felip Gálvez-Cancino,Georgia Stavrou,Gerasimos Mastrokalos,Helen Lowe,Ignacio Matos,James L. Reading,John A. Hartley,Kayalvizhi Selvaraju,Kezhong Chen,Leah Ensell,Mansi Shah,Marcos Vásquez,Maria Litovchenko,Olga Chervova,P. Pawlik,Robert E. Hynds,Saioa López,Samuel Gamble,Seng Kuong Anakin Ung,Supreet Kaur Bola,Thanos P. Mourikis,Victoria J. Spanswick,Yin Wu,Emilie Martinoni Hoogenboom,Fleur Monk,James W. Holding,Junaid Choudhary,Kunal Bhakhri,Marco Scarci,Martin Hayward,Νικόλαος Παναγιωτόπουλος,Pat Gorman,Robert Stephens,Steve Bandula,Yien Ning Sophia Wong,Tristan Clark,Heather Cheyne,Mohammed Khalil,Shirley Richardson,Tracey Cruickshank,Babu Naidu,Gurdeep Matharu,Jacqui A. Shaw,Joan Riley,Lindsay Primrose,John Le Quesne,Kevin G. Blyth,Alastair Kerr,Alexandra Clipson,Anshuman Chaturvedi,Caroline Dive,Dominic G. Rothwell,Elaine Kilgour,Jonathan Tugwood,Lynsey Priest,Pedro Oliveira,Philip Crosbie,Gillian Price,Judith Cave,Keith M. Kerr,Colin R. Lindsay,Fiona Blackhall,Matthew Krebs,Yvonne Summers,Alan Kirk,Mathew Thomas,Mo Asif,Nikos Kostoulas,Rocco Bilancia,Gary Middleton,Michael Shackcloth,Angela Leek,Jack Davies Hodgkinson,Nicola Totten,Craig Dick,Lily Robinson,Peter Russell,Madeleine Hewish,Sarah Danson,J.F. Lester,Fábio Gomes,Kate Brown,Mathew Carter,Akshay J. Patel,Aya Osman,Christer Lacson,Gerald Langman,Helen Shackleford,Madava Djearaman,Salma Kadiri,Aiman Alzetani,Jennifer Richards,Lydia Scarlett,Papawadee Ingram,Serena Chee,Silvia Austin,Amrita Bajaj,Apostolos Nakas,Azmina Sodha-Ramdeen,Dean A. Fennell,Keng Ang,Mohamad Tufail,Mohammed Fiyaz Chowdhry,Molly Scotland,Rebecca Boyles,Sridhar Rathinam,Claire Wilson,Domenic Marrone,Sean Dulloo,Ángeles Montero,Elaine Smith,Eustace Fontaine,Felice Granato,Helen Doran,Juliette Novasio,Kendadai Rammohan,Leena Dennis Joseph,Paul Bishop,Rajesh Shah,Stuart B. Moss,Vijay Joshi,Hugo J.W.L. Aerts,Tom L. Kaufmann,Roland F. Schwarz,Judit Kisistók,Mateo Sokač,Miklós Dióssy,Zoltán Szállási,Krijn K. Dijkstra,Yinyin Yuan,Fiona Byrne,Laura Amanda Boos,Benjamin Shum,Camille L. Gérard,Andreas M. Schmitt,Christina Messiou,David Cunningham,Ian Chau,Naureen Starling,Nicholas Turner,Liam Welsh,Robin L. Jones,Joanne Droney,Susana Banerjee,Kate Tatham,Shaman Jhanji,Kevin J. Harrington,Alicia Okines,Alison Reid,Kate Young,Andrew J.S. Furness,Lisa Pickering,Emma Nicholson,Sacheen Kumar,Katalin A. Wilkinson,Anthony Swerdlow,Robert J. Wilkinson,Crispin T. Hiley,Kevin Litchfield,Nicholas McGranahan,Mariam Jamal‐Hanjani,James Larkin,Se‐Hoon Lee,Samra Turajlic,Charles Swanton,Julian Downward,George Kassiotis
出处
期刊:Nature [Springer Nature]
卷期号:616 (7957): 563-573 被引量:69
标识
DOI:10.1038/s41586-023-05771-9
摘要

Abstract B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS) 1,2 . Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive 1,2 . Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma 3 . We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.
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