Using DNA sequencing data to quantify T cell fraction and therapy response

Accepted/In Press date: 10 August 2021

Published date: 8 September 2021

Additional Information: Funding Information: Competing interests D.A.M. reports speaker fees from AstraZeneca. M.A.B. has consulted for Achilles Therapeutics. R.R. has consulted for and has stock options in Achilles Therapeutics. K.L. has a patent on indel burden and CPI response pending and speaker fees from Roche tissue diagnostics, research funding from CRUK TDL/Ono/LifeArc alliance, and a consulting role with Monopteros Therapeutics. C.T.H. has received speaker fees from AstraZeneca. M.J.-H. is a member of the Scientific Advisory Board and Steering Committee for Achilles Therapeutics. N.M. has stock options in and has consulted for Achilles Therapeutics and holds a European patent in determining HLA LOH (PCT/GB2018/052004). C.S. acknowledges grant support from Pfizer, AstraZeneca, Bristol Myers Squibb, Roche-Ventana, Boehringer-Ingelheim, Archer Dx Inc. (collaboration in minimal residual disease sequencing technologies) and Ono Pharmaceutical; is an AstraZeneca Advisory Board Member and Chief Investigator for the MeRmaiD1 clinical trial; has consulted for Amgen, Pfizer, Novartis, GlaxoSmithKline, MSD, Bristol Myers Squibb, AstraZeneca, Illumina, Genentech, Roche-Ventana, GRAIL, Medicxi, Bicycle Therapeutics, Metabomed and the Sarah Cannon Research Institute; has stock options in Apogen Biotechnologies, Epic Bioscience and GRAIL; and has stock options and is co-founder of Achilles Therapeutics. C.S. holds patents relating to assay technology to detect tumour recurrence (PCT/GB2017/053289); to targeting neoantigens (PCT/EP2016/059401), identifying patent response to immune checkpoint blockade (PCT/EP2016/071471), determining HLA LOH (PCT/GB2018/052004), predicting survival rates of patients with cancer (PCT/GB2020/050221), to treating cancer by targeting Insertion/deletion mutations (PCT/GB2018/051893); identifying insertion/deletion mutation targets (PCT/GB2018/051892); methods for lung cancer detection (PCT/US2017/028013); and identifying responders to cancer treatment (PCT/GB2018/051912). Funding Information: Acknowledgements R.B. is supported by the NIHR BRC at University College London Hospitals. K.L. is funded by the UK Medical Research Council (MR/P014712/1 and MR/V033077/1), Rosetrees Trust and Cotswold Trust (A2437) and Cancer Research UK (C69256/A30194). T.B.K.W. is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001169), the UK Medical Research Council (FC001169) and the Wellcome Trust (FC001169) as well as the Marie Curie ITN Project PLOIDYNET (FP7-PEOPLE-2013, 607722), Breast Cancer Research Foundation (BCRF), Royal Society Research Professorships Enhancement Award (RP/EA/180007) and the Foulkes Foundation. E.L.L. receives funding from NovoNordisk Foundation (ID 16584). R.R. is supported by Royal Society Research Professorships Enhancement Award (RP/EA/180007). C.M.-R. is supported by Rosetrees. C.T.H. is supported by the NIHR BRC at University College London Hospitals. M.J.-H. has received funding from Cancer Research UK, National Institute for Health Research, Rosetrees Trust, UKI NETs and NIHR University College London Hospitals Biomedical Research Centre. N.M. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (Grant Number 211179/Z/18/Z) and also receives funding from Cancer Research UK, Rosetrees and the NIHR BRC at University College London Hospitals and the CRUK University College London Experimental Cancer Medicine Centre. C.S. is a Royal Society Napier Research Professor. His work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001169), the UK Medical Research Council (FC001169) and the Wellcome Trust (FC001169). C.S. is funded by Cancer Research UK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), Cancer Research UK Lung Cancer Centre of Excellence, the Rosetrees Trust, Butterfield and Stoneygate Trusts, NovoNordisk Foundation (ID16584), Royal Society Research Professorships Enhancement Award (RP/EA/180007), the NIHR BRC at University College London Hospitals, the CRUK-UCL Centre, Experimental Cancer Medicine Centre and the Breast Cancer Research Foundation (BCRF). This research is supported by a Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant (SU2C-AACR-DT23-17). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. C.S. also receives funding from the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007-2013) Consolidator Grant (FP7-THESEUS-617844), European Commission ITN (FP7-PloidyNet 607722), an ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (835297) and Chromavision from the European Union’s Horizon 2020 research and innovation programme (665233). The TRACERx study (Clinicaltrials.gov no: NCT01888601) is sponsored by University College London (UCL/12/0279) and has been approved by an independent Research Ethics Committee (13/LO/1546). TRACERx is funded by Cancer Research UK (C11496/A17786) and coordinated through the Cancer Research UK and UCL Cancer Trials Centre. The results published here are based in part on data generated by The Cancer Genome Atlas pilot project established by the NCI and the National Human Genome Research Institute. The data were Funding Information: retrieved through the database of Genotypes and Phenotypes (dbGaP) authorization (accession number phs000178.v9.p8). Information about TCGA and the constituent investigators and institutions of the TCGA research network can be found at http://cancergenome.nih.gov/. This project was enabled through access to the MRC eMedLab Medical Bioinformatics infrastructure, supported by the Medical Research Council (MR/L016311/1). In particular, we acknowledge the support of the High-Performance Computing at the Francis Crick Institute as well as the UCL Department of Computer Science Cluster and the support team. In addition, this work was supported by the CRUK City of London Centre Award (C7893/A26233). We thank all investigators, funders and industry partners that supported the generation of the data within this study, as well as patients for their participation. Specifically, we thank Merck & Co, Genentech and Bristol-Myers Squibb for generating the industry datasets used in this study, and E. Van Allen, L. Diaz, T. A. Chan, L. A. Garraway, R. S. Lo, D. F. Bajorin, D. Schadendorf, T. Powles, S.-H. Lee, A. Ribas and S. Ogawa for academic datasets. This work has been funded by Merck and Co. We gratefully acknowledge the patients and their families, the investigators and site personnel who participated in the KEYNOTE-001, -006, -012 and -028 studies. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature Limited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

Related URLs:

• http://www.scopus.com/inward/r...D=8YFLogxK
• https://discovery.ucl.ac.uk/id...616214.pdf

Local EPrints ID: 476444

URI: http://eprints.soton.ac.uk/id/eprint/476444

DOI: doi:10.1038/s41586-021-03894-5

ISSN: 0028-0836

PURE UUID: f0212f1a-493d-44ae-8344-040dd0b0b2db

Date deposited: 21 Apr 2023 12:08

Last modified: 17 Mar 2024 12:51