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Long-lasting multifunctional CD8(+) T cell responses in end-stage melanoma patients can be induced by dendritic cell vaccination

Cytotoxic T cells are considered crucial for antitumor immunity and their induction is the aim of various immunotherapeutic strategies. High frequencies of tumor-specific CD8(+) T cells alone, however, are no guarantee for long-term tumor control. Here, we analyzed the functionality of tumor-specifi...

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Autores principales: Wimmers, Florian, Aarntzen, Erik H. J. G., Duiveman-deBoer, Tjitske, Figdor, Carl G., Jacobs, Joannes F. M., Tel, Jurjen, de Vries, I. Jolanda M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760336/
https://www.ncbi.nlm.nih.gov/pubmed/26942087
http://dx.doi.org/10.1080/2162402X.2015.1067745
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author Wimmers, Florian
Aarntzen, Erik H. J. G.
Duiveman-deBoer, Tjitske
Figdor, Carl G.
Jacobs, Joannes F. M.
Tel, Jurjen
de Vries, I. Jolanda M.
author_facet Wimmers, Florian
Aarntzen, Erik H. J. G.
Duiveman-deBoer, Tjitske
Figdor, Carl G.
Jacobs, Joannes F. M.
Tel, Jurjen
de Vries, I. Jolanda M.
author_sort Wimmers, Florian
collection PubMed
description Cytotoxic T cells are considered crucial for antitumor immunity and their induction is the aim of various immunotherapeutic strategies. High frequencies of tumor-specific CD8(+) T cells alone, however, are no guarantee for long-term tumor control. Here, we analyzed the functionality of tumor-specific CD8(+) T cells in melanoma patients upon dendritic cell vaccination by measuring multiple T cell effector functions considered crucial for anticancer immunity, including the expression of pro-inflammatory cytokines, chemokines and cytotoxic markers (IFNγ, TNFα, IL-2, CCL4, CD107a). We identified small numbers of multifunctional (polyfunctional) tumor-specific CD8(+) T cells in several patients and dendritic cell therapy was able to improve the functionality of these pre-existing tumor-specific CD8(+) T cells. Generated multifunctional CD8(+) T cell responses could persist for up to ten years and within the same patient functionality could vary greatly for the different vaccination antigens. Importantly, after one cycle of DC vaccination highly functional CD8(+) T cells were only detected in patients displaying prolonged overall survival. Our results shed light on the dynamics of multifunctional tumor-specific CD8(+) T cells during metastatic melanoma and reveal a new feature of dendritic cell vaccination in vivo.
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spelling pubmed-47603362016-03-03 Long-lasting multifunctional CD8(+) T cell responses in end-stage melanoma patients can be induced by dendritic cell vaccination Wimmers, Florian Aarntzen, Erik H. J. G. Duiveman-deBoer, Tjitske Figdor, Carl G. Jacobs, Joannes F. M. Tel, Jurjen de Vries, I. Jolanda M. Oncoimmunology Original Research Cytotoxic T cells are considered crucial for antitumor immunity and their induction is the aim of various immunotherapeutic strategies. High frequencies of tumor-specific CD8(+) T cells alone, however, are no guarantee for long-term tumor control. Here, we analyzed the functionality of tumor-specific CD8(+) T cells in melanoma patients upon dendritic cell vaccination by measuring multiple T cell effector functions considered crucial for anticancer immunity, including the expression of pro-inflammatory cytokines, chemokines and cytotoxic markers (IFNγ, TNFα, IL-2, CCL4, CD107a). We identified small numbers of multifunctional (polyfunctional) tumor-specific CD8(+) T cells in several patients and dendritic cell therapy was able to improve the functionality of these pre-existing tumor-specific CD8(+) T cells. Generated multifunctional CD8(+) T cell responses could persist for up to ten years and within the same patient functionality could vary greatly for the different vaccination antigens. Importantly, after one cycle of DC vaccination highly functional CD8(+) T cells were only detected in patients displaying prolonged overall survival. Our results shed light on the dynamics of multifunctional tumor-specific CD8(+) T cells during metastatic melanoma and reveal a new feature of dendritic cell vaccination in vivo. Taylor & Francis 2015-08-12 /pmc/articles/PMC4760336/ /pubmed/26942087 http://dx.doi.org/10.1080/2162402X.2015.1067745 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License http://creativecommons.org/licenses/by-nc/3.0/, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Original Research
Wimmers, Florian
Aarntzen, Erik H. J. G.
Duiveman-deBoer, Tjitske
Figdor, Carl G.
Jacobs, Joannes F. M.
Tel, Jurjen
de Vries, I. Jolanda M.
Long-lasting multifunctional CD8(+) T cell responses in end-stage melanoma patients can be induced by dendritic cell vaccination
title Long-lasting multifunctional CD8(+) T cell responses in end-stage melanoma patients can be induced by dendritic cell vaccination
title_full Long-lasting multifunctional CD8(+) T cell responses in end-stage melanoma patients can be induced by dendritic cell vaccination
title_fullStr Long-lasting multifunctional CD8(+) T cell responses in end-stage melanoma patients can be induced by dendritic cell vaccination
title_full_unstemmed Long-lasting multifunctional CD8(+) T cell responses in end-stage melanoma patients can be induced by dendritic cell vaccination
title_short Long-lasting multifunctional CD8(+) T cell responses in end-stage melanoma patients can be induced by dendritic cell vaccination
title_sort long-lasting multifunctional cd8(+) t cell responses in end-stage melanoma patients can be induced by dendritic cell vaccination
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760336/
https://www.ncbi.nlm.nih.gov/pubmed/26942087
http://dx.doi.org/10.1080/2162402X.2015.1067745
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