Rapid and Continued T-Cell Differentiation into Long-term Effector and Memory Stem Cells in Vaccinated Melanoma Patients.

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Version: Author's accepted manuscript
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State: Public
Version: Supplementary document
Serval ID
serval:BIB_714D67883897
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Rapid and Continued T-Cell Differentiation into Long-term Effector and Memory Stem Cells in Vaccinated Melanoma Patients.
Journal
Clinical cancer research
Author(s)
Gannon P.O., Baumgaertner P., Huber A., Iancu E.M., Cagnon L., Abed Maillard S., Maby-El Hajjami H., Speiser D.E., Rufer N.
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Publication state
Published
Issued date
01/07/2017
Peer-reviewed
Oui
Volume
23
Number
13
Pages
3285-3296
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
<b>Purpose:</b> Patients with cancer benefit increasingly from T-cell-based therapies, such as adoptive T-cell transfer, checkpoint blockade, or vaccination. We have previously shown that serial vaccinations with Melan-A <sup>MART-1</sup> <sub>26-35</sub> peptide, CpG-B, and incomplete Freund adjuvant (IFA) generated robust tumor-specific CD8 T-cell responses in patients with melanoma. Here, we describe the detailed kinetics of early- and long-term establishment of T-cell frequency, differentiation (into memory and effector cells), polyfunctionality, and clonotype repertoire induced by vaccination. <b>Experimental Design:</b> Twenty-nine patients with melanoma were treated with multiple monthly subcutaneous vaccinations consisting of CpG-B, and either the native/EAA ( <i>n</i> = 13) or the analogue/ELA ( <i>n</i> = 16) Melan-A <sup>MART-1</sup> <sub>26-35</sub> peptide emulsified in IFA. Phenotypes and functionality of circulating Melan-A-specific CD8 T cells were assessed directly <i>ex vivo</i> by multiparameter flow cytometry, and TCR clonotypes were determined <i>ex vivo</i> by mRNA transcript analyses of individually sorted cells. <b>Results:</b> Our results highlight the determining impact of the initial vaccine injections on the rapid and strong induction of differentiated effector T cells in both patient cohorts. Moreover, long-term polyfunctional effector T-cell responses were associated with expansion of stem cell-like memory T cells over time along vaccination. Dominant TCR clonotypes emerged early and persisted throughout the entire period of observation. Interestingly, one highly dominant clonotype was found shared between memory and effector subsets. <b>Conclusions:</b> Peptide/CpG-B/IFA vaccination induced powerful long-term T-cell responses with robust effector cells and stem cell-like memory cells. These results support the further development of CpG-B-based cancer vaccines, either alone or as specific component of combination therapies. <i>Clin Cancer Res; 23(13); 3285-96. ©2016 AACR</i> .
Keywords
Adoptive Transfer, Antigens, Neoplasm/immunology, Antigens, Neoplasm/therapeutic use, CD8-Positive T-Lymphocytes/drug effects, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines/immunology, Cancer Vaccines/therapeutic use, Cell Differentiation/drug effects, Cell Differentiation/immunology, Freund's Adjuvant/immunology, Freund's Adjuvant/therapeutic use, HLA-A2 Antigen/immunology, Humans, Immunologic Memory/drug effects, Lipids/immunology, Lipids/therapeutic use, Lymphocyte Activation/drug effects, Lymphocyte Activation/immunology, MART-1 Antigen/immunology, MART-1 Antigen/therapeutic use, Melanoma/immunology, Melanoma/pathology, Melanoma/therapy, Stem Cells/drug effects, Stem Cells/immunology, T-Lymphocytes/immunology
Pubmed
Web of science
Open Access
Yes
Create date
05/12/2016 22:20
Last modification date
20/08/2019 15:29
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