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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Antibodies against endogenous retroviruses promote lung cancer immunotherapy
Nature, Volume 616, No. 7957, Year 2023
Notification
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Description
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 elusive1,2. 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 adenocarcinoma3. 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. © 2023, The Author(s).
Authors & Co-Authors
Ng, Kevin W.
United Kingdom, London
The Francis Crick Institute
Salgado, Roberto A.
Belgium, Antwerpen
Zas Hospitals
Australia, Melbourne
Peter Maccallum Cancer Centre
Fendler, Annika
United Kingdom, London
The Francis Crick Institute
Au, Lewis
United Kingdom, London
The Francis Crick Institute
United Kingdom, London
The Royal Marsden Hospital
Shepherd, Scott T.C.
United Kingdom, London
The Francis Crick Institute
United Kingdom, London
The Royal Marsden Hospital
Faulkner, Nikhil
United Kingdom, London
The Francis Crick Institute
United Kingdom, London
Imperial College London
Wilson, Gareth A.
United Kingdom, London
The Francis Crick Institute
Cook, Daniel E.
United Kingdom, London
The Francis Crick Institute
Yousaf, Nadia
United Kingdom, London
The Royal Marsden Hospital
Popat, Sanjay
United Kingdom, London
The Royal Marsden Hospital
United Kingdom, London
The Institute of Cancer Research
Hackshaw, Allan K.
United Kingdom, London
University College London
Al-Sawaf, Othman
United Kingdom, London
The Francis Crick Institute
United Kingdom, London
University College London
Rosenthal, Rachel
United Kingdom, London
The Francis Crick Institute
Nicod, Jérôme
United Kingdom, London
The Francis Crick Institute
Forster, Martin David
United Kingdom, London
Ucl Cancer Institute
Quezada, Sergio A.
United Kingdom, London
University College London
Wilson, James Gaines
United Kingdom, London
Ucl Cancer Institute
Marafioti, Teresa
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
Nicholson, Andrew Gordon
United Kingdom, London
Imperial College London
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Lim, Eric Tien Siang
United Kingdom, London
Imperial College London
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Herrero, Javier
United Kingdom, London
University College London
Van Loo, Peter
United Kingdom, London
The Francis Crick Institute
United States, Houston
The University of Texas Md Anderson Cancer Center
Nair, Arjun
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
United Kingdom, London
University College London
Navani, Neal
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
United Kingdom, London
University College London
Patrini, Davide
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
Nye, Emma L.
United Kingdom, London
The Francis Crick Institute
Stone, Richard Kevin
United Kingdom, London
The Francis Crick Institute
Chuter, David J.
Unknown Affiliation
Fraioli, Francesco
United Kingdom, London
University College London
Janes, Sam M.
United Kingdom, London
University College London
Tanić, Miljana
United Kingdom, London
University College London
Serbia, Belgrade
Institute of Oncology and Radiology of Serbia
Devaraj, Anand A.
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Grönroos, Eva
United Kingdom, London
The Francis Crick Institute
Hobson, Philip
United Kingdom, London
The Francis Crick Institute
Zhang, Hanyun
United Kingdom, London
The Institute of Cancer Research
Hartley, John A.
United Kingdom, London
University College London
Litovchenko, Maria
United Kingdom, London
University College London
López, Saioa
United Kingdom, London
University College London
Scarci, Marco
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
Clark, Tristan
United Kingdom, London
University College London
Naidu, Babu V.
United Kingdom, Birmingham
University of Birmingham
Primrose, Lindsay
United Kingdom, Leicester
University of Leicester
Le Quesne, John P.C.
United Kingdom, Glasgow
Beatson Institute for Cancer Research
United Kingdom, Glasgow
Nhs Greater Glasgow and Clyde
United Kingdom, Glasgow
University of Glasgow
Blyth, Kevin G.
United Kingdom, Glasgow
Beatson Institute for Cancer Research
United Kingdom, Glasgow
University of Glasgow
United Kingdom, Glasgow
Queen Elizabeth University Hospital, Glasgow
Tugwood, Jonathan D.
United Kingdom, Manchester
The University of Manchester
Kerr, Keith M.
United Kingdom, Aberdeen
University of Aberdeen
United Kingdom, Aberdeen
Nhs Grampian
Blackhall, Fiona Helen
United Kingdom, Manchester
The University of Manchester
Middleton, Gary W.
United Kingdom, Birmingham
University of Birmingham
United Kingdom, Birmingham
University Hospitals Birmingham Nhs Foundation Trust
Shackcloth, Michael J.
United Kingdom, Liverpool
Liverpool Heart and Chest Hospital
Danson, Sarah J.
United Kingdom, Sheffield
Sheffield Teaching Hospitals Nhs Foundation Trust
Gomes, Fábio
United Kingdom, Manchester
The Christie Nhs Foundation Trust
Brown, Katherine M.
United Kingdom, Manchester
The Christie Nhs Foundation Trust
Patel, Akshay Jatin
United Kingdom, Birmingham
University Hospitals Birmingham Nhs Foundation Trust
Bajaj, Amrita
United Kingdom, Leicester
University Hospitals of Leicester Nhs Trust
Nakas, Apostolos
United Kingdom, Leicester
University Hospitals of Leicester Nhs Trust
Fennell, Dean Andrew
United Kingdom, Leicester
University Hospitals of Leicester Nhs Trust
United Kingdom, Leicester
University of Leicester
Fontaine, Eustace J.
United Kingdom, Manchester
Manchester University Nhs Foundation Trust
Rammohan, Kandadai Seshadri
United Kingdom, Manchester
Manchester University Nhs Foundation Trust
Yuan, Yinyin
United States, Houston
The University of Texas Md Anderson Cancer Center
Byrne, Fiona
United Kingdom, London
The Francis Crick Institute
Boos, Laura Amanda
United Kingdom, London
The Royal Marsden Hospital
Shum, Benjamin
United Kingdom, London
The Francis Crick Institute
United Kingdom, London
The Royal Marsden Hospital
Gérard, Camille Lea
United Kingdom, London
The Francis Crick Institute
Schmitt, Andreas Michael
United Kingdom, London
The Royal Marsden Hospital
Messiou, Christina
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Cunningham, David C.
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Chau, Ian Yin Yan
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Starling, Naureen
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Turner, Nicholas C.
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
United Kingdom, London
The Institute of Cancer Research
Welsh, Liam C.
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Droney, Joanne M.
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Banerjee, Susana N.
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Tatham, Kate Colette
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
United Kingdom, London
Imperial College London
Jhanji, Shaman
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Harrington, Kevin J.
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
United Kingdom, London
The Institute of Cancer Research
Okines, Alicia F.C.
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Reid, Alison H.M.
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Young, Kathleen
United Kingdom, London
The Royal Marsden Hospital
Furness, Andrew J.S.
United Kingdom, London
The Royal Marsden Hospital
Pickering, Lisa M.
United Kingdom, London
The Royal Marsden Hospital
Nicholson, Emma Kate
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Kumar, Sacheen
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
Andrea Wilkinson, Katalin Andrea
United Kingdom, London
The Royal Marsden Nhs Foundation Trust
United Kingdom, London
The Francis Crick Institute
Swerdlow, Anthony J.
United Kingdom, London
The Institute of Cancer Research
Wilkinson, Robert John
United Kingdom, London
Imperial College London
United Kingdom, London
The Francis Crick Institute
South Africa, Cape Town
Wellcome Centre for Infectious Diseases Research in Africa
Litchfield, Kevin
United Kingdom, London
University College London
Larkin, James M.G.
United Kingdom, London
The Royal Marsden Hospital
United Kingdom, London
The Institute of Cancer Research
Turajlic, Samra
United Kingdom, London
The Francis Crick Institute
United Kingdom, London
The Royal Marsden Hospital
United Kingdom, London
The Institute of Cancer Research
Swanton, Charles
United Kingdom, London
The Francis Crick Institute
United Kingdom, London
Ucl Cancer Institute
Kassiotis, George
United Kingdom, London
The Francis Crick Institute
United Kingdom, London
Imperial College London
Statistics
Citations: 25
Authors: 90
Affiliations: 52
Identifiers
Doi:
10.1038/s41586-023-05771-9
ISSN:
00280836
Research Areas
Cancer
Health System And Policy
Study Design
Cohort Study