Antibodies against endogenous retroviruses promote lung cancer immunotherapy.

Autor:	Ng KW; Retroviral Immunology Laboratory, The Francis Crick Institute, London, UK., Boumelha J; Oncogene Biology Laboratory, The Francis Crick Institute, London, UK., Enfield KSS; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Almagro J; Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK., Cha H; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Pich O; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Karasaki T; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK., Moore DA; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Department of Cellular Pathology, University College London Hospitals, London, UK., Salgado R; Department of Pathology, ZAS Hospitals, Antwerp, Belgium.; Division of Research, Peter MacCallum Cancer Centre, Melbourne, Queensland, Australia., Sivakumar M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Young G; Retroviral Immunology Laboratory, The Francis Crick Institute, London, UK.; Bioinformatics and Biostatistics Facility, The Francis Crick Institute, London, UK., Molina-Arcas M; Oncogene Biology Laboratory, The Francis Crick Institute, London, UK., de Carné Trécesson S; Oncogene Biology Laboratory, The Francis Crick Institute, London, UK., Anastasiou P; Oncogene Biology Laboratory, The Francis Crick Institute, London, UK., Fendler A; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK., Au L; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK.; Renal and Skin Units, The Royal Marsden Hospital, London, UK., Shepherd STC; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK.; Renal and Skin Units, The Royal Marsden Hospital, London, UK., Martínez-Ruiz C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Puttick C; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Black JRM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Watkins TBK; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Kim H; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Shim S; Department of Health Sciences and Technology, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea., Faulkner N; Retroviral Immunology Laboratory, The Francis Crick Institute, London, UK.; National Heart and Lung Institute, Imperial College London, London, UK., Attig J; Retroviral Immunology Laboratory, The Francis Crick Institute, London, UK., Veeriah S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Magno N; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Ward S; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Advanced Sequencing Facility, The Francis Crick Institute, London, UK., Frankell AM; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Al Bakir M; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Lim EL; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Hill MS; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Wilson GA; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Cook DE; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Birkbak NJ; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark., Behrens A; Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK.; Cancer Stem Cell Laboratory, Institute of Cancer Research, London, UK.; Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK.; CRUK Convergence Science Centre, Imperial College, London, UK., Yousaf N; Renal and Skin Units, The Royal Marsden Hospital, London, UK.; Lung Unit, The Royal Marsden Hospital, London, UK., Popat S; Lung Unit, The Royal Marsden Hospital, London, UK.; Division of Clinical Studies, The Institute of Cancer Research, London, UK., Hackshaw A; Cancer Research UK and University College London Cancer Trials Centre, London, UK., Hiley CT; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Litchfield K; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Tumour Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, London, UK., McGranahan N; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Jamal-Hanjani M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.; Department of Oncology, University College London Hospitals, London, UK., Larkin J; Renal and Skin Units, The Royal Marsden Hospital, London, UK.; Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London, UK., Lee SH; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.; Department of Health Sciences and Technology, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea., Turajlic S; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK.; Renal and Skin Units, The Royal Marsden Hospital, London, UK.; Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London, UK., Swanton C; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK. charles.swanton@crick.ac.uk.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. charles.swanton@crick.ac.uk.; Department of Oncology, University College London Hospitals, London, UK. charles.swanton@crick.ac.uk., Downward J; Oncogene Biology Laboratory, The Francis Crick Institute, London, UK. julian.downward@crick.ac.uk., Kassiotis G; Retroviral Immunology Laboratory, The Francis Crick Institute, London, UK. george.kassiotis@crick.ac.uk.; Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK. george.kassiotis@crick.ac.uk.
Jazyk:	angličtina
Zdroj:	Nature [Nature] 2023 Apr; Vol. 616 (7957), pp. 563-573. Date of Electronic Publication: 2023 Apr 12.
DOI:	10.1038/s41586-023-05771-9
Abstrakt:	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. (© 2023. The Author(s).)
Databáze:	MEDLINE
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