Frontiers in Immunology (Nov 2020)
Tumor Infiltrating Effector Memory Antigen-Specific CD8+ T Cells Predict Response to Immune Checkpoint Therapy
- Nicola Principe,
- Nicola Principe,
- Joel Kidman,
- Joel Kidman,
- Siting Goh,
- Caitlin M. Tilsed,
- Caitlin M. Tilsed,
- Scott A. Fisher,
- Scott A. Fisher,
- Vanessa S. Fear,
- Catherine A. Forbes,
- Rachael M. Zemek,
- Abha Chopra,
- Mark Watson,
- Ian M. Dick,
- Ian M. Dick,
- Louis Boon,
- Robert A. Holt,
- Richard A. Lake,
- Richard A. Lake,
- Anna K. Nowak,
- Anna K. Nowak,
- Willem Joost Lesterhuis,
- Willem Joost Lesterhuis,
- Willem Joost Lesterhuis,
- Alison M. McDonnell,
- Alison M. McDonnell,
- Alison M. McDonnell,
- Jonathan Chee,
- Jonathan Chee
Affiliations
- Nicola Principe
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
- Nicola Principe
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
- Joel Kidman
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
- Joel Kidman
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
- Siting Goh
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
- Caitlin M. Tilsed
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
- Caitlin M. Tilsed
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
- Scott A. Fisher
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
- Scott A. Fisher
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
- Vanessa S. Fear
- Telethon Kids Institute, Perth, WA, Australia
- Catherine A. Forbes
- Telethon Kids Institute, Perth, WA, Australia
- Rachael M. Zemek
- Telethon Kids Institute, Perth, WA, Australia
- Abha Chopra
- Institute of Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia
- Mark Watson
- Institute of Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia
- Ian M. Dick
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
- Ian M. Dick
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
- Louis Boon
- Polpharma Biologics, Utrecht, Netherlands
- Robert A. Holt
- BC Cancer Agency, Vancouver, BC, Canada
- Richard A. Lake
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
- Richard A. Lake
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
- Anna K. Nowak
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
- Anna K. Nowak
- School of Medicine, University of Western Australia, Crawley, WA, Australia
- Willem Joost Lesterhuis
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
- Willem Joost Lesterhuis
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
- Willem Joost Lesterhuis
- Telethon Kids Institute, Perth, WA, Australia
- Alison M. McDonnell
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
- Alison M. McDonnell
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
- Alison M. McDonnell
- Telethon Kids Institute, Perth, WA, Australia
- Jonathan Chee
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia
- Jonathan Chee
- School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia
- DOI
- https://doi.org/10.3389/fimmu.2020.584423
- Journal volume & issue
-
Vol. 11
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.
Keywords
- immune checkpoint therapy
- tumor-specific T cells
- TCR repertoire
- cytotoxic T lymphocytes
- effector memory
