학술논문
Immune checkpoint therapy responders display early clonal expansion of tumor infiltrating lymphocytes.
Document Type
Academic Journal
Author
Kidman J; National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Perth, Australia.; Zemek RM; Telethon Kids Institute, Perth, Australia.; Sidhom JW; Icahn School of Medicine, Mt Sinai Hospital, New York, USA.; Correa D; Complex Systems Group, Department of Mathematics and Statistics, University of Western Australia, Perth, Australia.; Principe N; National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Perth, Australia.; Sheikh F; National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Perth, Australia.; Fear VS; Telethon Kids Institute, Perth, Australia.; Forbes CA; Telethon Kids Institute, Perth, Australia.; Chopra A; Medical Genomics Laboratories (IIID), Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Murdoch, Australia.; Boon L; JJP Biologics, Warsaw, Poland.; Zaitouny A; Complex Systems Group, Department of Mathematics and Statistics, University of Western Australia, Perth, Australia.; Department of Mathematical Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.; de Jong E; Telethon Kids Institute, Perth, Australia.; Medical School, University of Western Australia, Perth, Australia.; Holt RA; BC Cancer Research Institute, Vancouver, Canada.; Jones M; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Australia.; Millward MJ; Medical School, University of Western Australia, Perth, Australia.; Lassmann T; Telethon Kids Institute, Perth, Australia.; Forrest ARR; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Australia.; Nowak AK; National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Perth, Australia.; Medical School, University of Western Australia, Perth, Australia.; Watson M; Medical Genomics Laboratories (IIID), Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Murdoch, Australia.; Lake RA; National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Perth, Australia.; Lesterhuis WJ; National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Perth, Australia.; Telethon Kids Institute, Perth, Australia.; Chee J; National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Perth, Australia.
Source
Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101570526 Publication Model: eCollection Cited Medium: Internet ISSN: 2162-402X (Electronic) Linking ISSN: 21624011 NLM ISO Abbreviation: Oncoimmunology Subsets: MEDLINE
Subject
Language
English
Abstract
Immune checkpoint therapy (ICT) causes durable tumour responses in a subgroup of patients, but it is not well known how T cell receptor beta (TCRβ) repertoire dynamics contribute to the therapeutic response. Using murine models that exclude variation in host genetics, environmental factors and tumour mutation burden, limiting variation between animals to naturally diverse TCRβ repertoires, we applied TCRseq, single cell RNAseq and flow cytometry to study TCRβ repertoire dynamics in ICT responders and non-responders. Increased oligoclonal expansion of TCRβ clonotypes was observed in responding tumours. Machine learning identified TCRβ CDR3 signatures unique to each tumour model, and signatures associated with ICT response at various timepoints before or during ICT. Clonally expanded CD8+ T cells in responding tumours post ICT displayed effector T cell gene signatures and phenotype. An early burst of clonal expansion during ICT is associated with response, and we report unique dynamics in TCRβ signatures associated with ICT response.
Competing Interests: LB is employed by the company JJP Biologics. WJL received research funding from Douglas Pharmaceuticals, AstraZeneca, ENA therapeutics, consultancy for Douglas Pharmaceuticals and MSD. AN is on the advisory board of Boehringer Ingelheim, Bayer, Roche, BMS; and received research funding from AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Competing Interests: LB is employed by the company JJP Biologics. WJL received research funding from Douglas Pharmaceuticals, AstraZeneca, ENA therapeutics, consultancy for Douglas Pharmaceuticals and MSD. AN is on the advisory board of Boehringer Ingelheim, Bayer, Roche, BMS; and received research funding from AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)