Journal article
Tumor infiltrating effector memory Antigen-Specific CD8+ T Cells predict response to immune checkpoint therapy
Frontiers in Immunology, Vol.11, Art. 584423
2020
Abstract
Immune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICT that correlate with successful responses have not been well characterized. Here, we studied murine tumor models with dichotomous responses to ICT. We tracked tumor antigen-specific CTL frequencies and phenotype before and after ICT in responding and non-responding animals. Tumor antigen-specific CTLs increased within tumor and draining lymph nodes after ICT, and exhibited an effector memory-like phenotype, expressing IL-7R (CD127), KLRG1, T-bet, and granzyme B. Responding tumors exhibited higher infiltration of effector memory tumor antigen-specific CTLs, but lower frequencies of regulatory T cells compared to non-responders. Tumor antigen-specific CTLs persisted in responding animals and formed memory responses against tumor antigens. Our results suggest that increased effector memory tumor antigen-specific CTLs, in the presence of reduced immunosuppression within tumors is part of a successful ICT response. Temporal and nuanced analysis of T cell subsets provides a potential new source of immune based biomarkers for response to ICT.
Details
- Title
- Tumor infiltrating effector memory Antigen-Specific CD8+ T Cells predict response to immune checkpoint therapy
- Authors/Creators
- N. Principe (Author/Creator) - The University of Western AustraliaJ. Kidman (Author/Creator) - The University of Western AustraliaS. Goh (Author/Creator) - The University of Western AustraliaC.M. Tilsed (Author/Creator) - The University of Western AustraliaS.A. Fisher (Author/Creator) - The University of Western AustraliaV.S. Fear (Author/Creator) - The Kids Research Institute AustraliaC.A. Forbes (Author/Creator) - The Kids Research Institute AustraliaR.M. Zemek (Author/Creator) - The Kids Research Institute AustraliaA. Chopra (Author/Creator) - Murdoch UniversityM. Watson (Author/Creator) - Murdoch UniversityI.M. Dick (Author/Creator) - The University of Western AustraliaL. Boon (Author/Creator) - Polpharma Biologics (Netherlands)R.A. Holt (Author/Creator) - BC Cancer AgencyR.A. Lake (Author/Creator) - The University of Western AustraliaA.K. Nowak (Author/Creator) - The University of Western AustraliaW.J. Lesterhuis (Author/Creator) - The University of Western AustraliaA.M. McDonnell (Author/Creator) - The University of Western AustraliaJ. Chee (Author/Creator) - The University of Western Australia
- Publication Details
- Frontiers in Immunology, Vol.11, Art. 584423
- Publisher
- Frontiers Media
- Identifiers
- 991005544163807891
- Copyright
- © 2020 The Authors.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- 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
- ESI research areas
- Immunology