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Published (Version of Record)CC BY V4.0, Open Access
Journal article
Immune checkpoint therapy responders display early clonal expansion of tumor infiltrating lymphocytes
Oncoimmunology, Vol.13(1), 2345859
2024
PMCID: PMC11057660
PMID: 38686178
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.
Details
- Title
- Immune checkpoint therapy responders display early clonal expansion of tumor infiltrating lymphocytes
- Authors/Creators
- Joel Kidman - Institute for Respiratory HealthRachael M. Zemek - The Kids Research Institute AustraliaJohn-William Sidhom - Mount Sinai HospitalDebora Correa - The University of Western AustraliaNicola Principe - Institute for Respiratory HealthFezaan Sheikh - Institute for Respiratory HealthVanessa S. Fear - The Kids Research Institute AustraliaCatherine A. Forbes - The Kids Research Institute AustraliaAbha Chopra - Murdoch UniversityLouis Boon - , ,Ayham Zaitouny - The University of Western AustraliaEmma de Jong - The Kids Research Institute AustraliaRobert A. Holt - , ,Matt Jones - Harry Perkins Institute of Medical ResearchMichael J. Millward - The University of Western AustraliaTimo Lassmann - The Kids Research Institute AustraliaAlistair R.R. Forrest - Harry Perkins Institute of Medical ResearchAnna K. Nowak - Institute for Respiratory HealthMark Watson - Murdoch UniversityRichard A. Lake - Institute for Respiratory HealthW. Joost Lesterhuis - The Kids Research Institute AustraliaJonathan Chee - Institute for Respiratory Health
- Publication Details
- Oncoimmunology, Vol.13(1), 2345859
- Publisher
- Taylor & Francis Group
- Identifiers
- 991005656603807891
- Copyright
- © 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.214 Checkpoint Inhibition
- Web Of Science research areas
- Immunology
- Oncology
- ESI research areas
- Biology & Biochemistry