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Tumor Infiltrating Effector Memory Antigen-Specific CD8(+) T Cells Predict Response to Immune Checkpoint Therapy

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 b...

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Autores principales: Principe, Nicola, Kidman, Joel, Goh, Siting, Tilsed, Caitlin M., Fisher, Scott A., Fear, Vanessa S., Forbes, Catherine A., Zemek, Rachael M., Chopra, Abha, Watson, Mark, Dick, Ian M., Boon, Louis, Holt, Robert A., Lake, Richard A., Nowak, Anna K., Lesterhuis, Willem Joost, McDonnell, Alison M., Chee, Jonathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688517/
https://www.ncbi.nlm.nih.gov/pubmed/33262762
http://dx.doi.org/10.3389/fimmu.2020.584423
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author Principe, Nicola
Kidman, Joel
Goh, Siting
Tilsed, Caitlin M.
Fisher, Scott A.
Fear, Vanessa S.
Forbes, Catherine A.
Zemek, Rachael M.
Chopra, Abha
Watson, Mark
Dick, Ian M.
Boon, Louis
Holt, Robert A.
Lake, Richard A.
Nowak, Anna K.
Lesterhuis, Willem Joost
McDonnell, Alison M.
Chee, Jonathan
author_facet Principe, Nicola
Kidman, Joel
Goh, Siting
Tilsed, Caitlin M.
Fisher, Scott A.
Fear, Vanessa S.
Forbes, Catherine A.
Zemek, Rachael M.
Chopra, Abha
Watson, Mark
Dick, Ian M.
Boon, Louis
Holt, Robert A.
Lake, Richard A.
Nowak, Anna K.
Lesterhuis, Willem Joost
McDonnell, Alison M.
Chee, Jonathan
author_sort Principe, Nicola
collection PubMed
description 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.
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spelling pubmed-76885172020-11-30 Tumor Infiltrating Effector Memory Antigen-Specific CD8(+) T Cells Predict Response to Immune Checkpoint Therapy Principe, Nicola Kidman, Joel Goh, Siting Tilsed, Caitlin M. Fisher, Scott A. Fear, Vanessa S. Forbes, Catherine A. Zemek, Rachael M. Chopra, Abha Watson, Mark Dick, Ian M. Boon, Louis Holt, Robert A. Lake, Richard A. Nowak, Anna K. Lesterhuis, Willem Joost McDonnell, Alison M. Chee, Jonathan Front Immunol Immunology 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. Frontiers Media S.A. 2020-11-12 /pmc/articles/PMC7688517/ /pubmed/33262762 http://dx.doi.org/10.3389/fimmu.2020.584423 Text en Copyright © 2020 Principe, Kidman, Goh, Tilsed, Fisher, Fear, Forbes, Zemek, Chopra, Watson, Dick, Boon, Holt, Lake, Nowak, Lesterhuis, McDonnell and Chee http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Principe, Nicola
Kidman, Joel
Goh, Siting
Tilsed, Caitlin M.
Fisher, Scott A.
Fear, Vanessa S.
Forbes, Catherine A.
Zemek, Rachael M.
Chopra, Abha
Watson, Mark
Dick, Ian M.
Boon, Louis
Holt, Robert A.
Lake, Richard A.
Nowak, Anna K.
Lesterhuis, Willem Joost
McDonnell, Alison M.
Chee, Jonathan
Tumor Infiltrating Effector Memory Antigen-Specific CD8(+) T Cells Predict Response to Immune Checkpoint Therapy
title Tumor Infiltrating Effector Memory Antigen-Specific CD8(+) T Cells Predict Response to Immune Checkpoint Therapy
title_full Tumor Infiltrating Effector Memory Antigen-Specific CD8(+) T Cells Predict Response to Immune Checkpoint Therapy
title_fullStr Tumor Infiltrating Effector Memory Antigen-Specific CD8(+) T Cells Predict Response to Immune Checkpoint Therapy
title_full_unstemmed Tumor Infiltrating Effector Memory Antigen-Specific CD8(+) T Cells Predict Response to Immune Checkpoint Therapy
title_short Tumor Infiltrating Effector Memory Antigen-Specific CD8(+) T Cells Predict Response to Immune Checkpoint Therapy
title_sort tumor infiltrating effector memory antigen-specific cd8(+) t cells predict response to immune checkpoint therapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688517/
https://www.ncbi.nlm.nih.gov/pubmed/33262762
http://dx.doi.org/10.3389/fimmu.2020.584423
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