dc.contributor.author | Ng, KW | |
dc.contributor.author | Boumelha, J | |
dc.contributor.author | Enfield, KSS | |
dc.contributor.author | Almagro, J | |
dc.contributor.author | Cha, H | |
dc.contributor.author | Pich, O | |
dc.contributor.author | Karasaki, T | |
dc.contributor.author | Moore, DA | |
dc.contributor.author | Salgado, R | |
dc.contributor.author | Sivakumar, M | |
dc.contributor.author | Young, G | |
dc.contributor.author | Molina-Arcas, M | |
dc.contributor.author | de Carné Trécesson, S | |
dc.contributor.author | Anastasiou, P | |
dc.contributor.author | Fendler, A | |
dc.contributor.author | Au, L | |
dc.contributor.author | Shepherd, STC | |
dc.contributor.author | Martínez-Ruiz, C | |
dc.contributor.author | Puttick, C | |
dc.contributor.author | Black, JRM | |
dc.contributor.author | Watkins, TBK | |
dc.contributor.author | Kim, H | |
dc.contributor.author | Shim, S | |
dc.contributor.author | Faulkner, N | |
dc.contributor.author | Attig, J | |
dc.contributor.author | Veeriah, S | |
dc.contributor.author | Magno, N | |
dc.contributor.author | Ward, S | |
dc.contributor.author | Frankell, AM | |
dc.contributor.author | Al Bakir, M | |
dc.contributor.author | Lim, EL | |
dc.contributor.author | Hill, MS | |
dc.contributor.author | Wilson, GA | |
dc.contributor.author | Cook, DE | |
dc.contributor.author | Birkbak, NJ | |
dc.contributor.author | Behrens, A | |
dc.contributor.author | Yousaf, N | |
dc.contributor.author | Popat, S | |
dc.contributor.author | Hackshaw, A | |
dc.contributor.author | TRACERx Consortium, | |
dc.contributor.author | CAPTURE Consortium, | |
dc.contributor.author | Hiley, CT | |
dc.contributor.author | Litchfield, K | |
dc.contributor.author | McGranahan, N | |
dc.contributor.author | Jamal-Hanjani, M | |
dc.contributor.author | Larkin, J | |
dc.contributor.author | Lee, S-H | |
dc.contributor.author | Turajlic, S | |
dc.contributor.author | Swanton, C | |
dc.contributor.author | Downward, J | |
dc.contributor.author | Kassiotis, G | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2023-06-23T13:13:52Z | |
dc.date.available | 2023-06-23T13:13:52Z | |
dc.date.issued | 2023-04-20 | |
dc.identifier | 10.1038/s41586-023-05771-9 | |
dc.identifier.citation | Nature, 2023, 616 (7957), pp. 563 - 573 | |
dc.identifier.issn | 0028-0836 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5856 | |
dc.identifier.eissn | 1476-4687 | |
dc.identifier.eissn | 1476-4687 | |
dc.identifier.doi | 10.1038/s41586-023-05771-9 | |
dc.description.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 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 563 - 573 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.relation.ispartof | Nature | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Adenocarcinoma of Lung | |
dc.subject | Carcinoma, Non-Small-Cell Lung | |
dc.subject | Disease Models, Animal | |
dc.subject | Endogenous Retroviruses | |
dc.subject | Immunotherapy | |
dc.subject | Lung | |
dc.subject | Lung Neoplasms | |
dc.subject | Tumor Microenvironment | |
dc.subject | B-Lymphocytes | |
dc.subject | Cohort Studies | |
dc.subject | Antibodies | |
dc.title | Antibodies against endogenous retroviruses promote lung cancer immunotherapy. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-01-30 | |
dc.date.updated | 2023-06-23T13:13:10Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41586-023-05771-9 | |
rioxxterms.licenseref.startdate | 2023-04-20 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37046094 | |
pubs.issue | 7957 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Lung Cancer Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology/Thoracic Oncology (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Lung Cancer Group | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41586-023-05771-9 | |
pubs.volume | 616 | |
icr.researchteam | Convergence SC Management | |
icr.researchteam | Lung Cancer Group | |
dc.contributor.icrauthor | Behrens, Axel | |
icr.provenance | Deposited by Mr Arek Surman on 2023-06-23. Deposit type is initial. No. of files: 1. Files: Antibodies against endogenous retroviruses promote lung cancer immunotherapy.pdf | |