Tumor infiltrating effector memory Antigen-Specific CD8+ T Cells predict response to immune checkpoint therapy

Principe, N., Kidman, J., Goh, S., Tilsed, C.M., Fisher, S.A., Fear, V.S., Forbes, C.A., Zemek, R.M., Chopra, A., Watson, M.ORCID: 0000-0002-6438-9225, Dick, I.M., Boon, L., Holt, R.A., Lake, R.A., Nowak, A.K., Lesterhuis, W.J., McDonnell, A.M. and Chee, J. (2020) Tumor infiltrating effector memory Antigen-Specific CD8+ T Cells predict response to immune checkpoint therapy. Frontiers in Immunology, 11 . Art. 584423.

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.

Item Type:	Journal Article
Murdoch Affiliation(s):	Institute for Immunology and Infectious Diseases
Publisher:	Frontiers Media
Copyright:	© 2020 The Authors.
United Nations SDGs:	Goal 3: Good Health and Well-Being
URI:	http://researchrepository.murdoch.edu.au/id/eprint/58972

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