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Vaccination with High-Affinity Epitopes Impairs Antitumor Efficacy by Increasing PD-1 Expression on CD8 + T Cells.
- Source :
-
Cancer immunology research [Cancer Immunol Res] 2017 Aug; Vol. 5 (8), pp. 630-641. Date of Electronic Publication: 2017 Jun 20. - Publication Year :
- 2017
-
Abstract
- Antitumor vaccines encoding self-antigens generally have low immunogenicity in clinical trials. Several approaches are aimed at improving vaccine immunogenicity, including efforts to alter encoded epitopes. Immunization with epitopes altered for increased affinity for the major histocompatibility complex (MHC) or T-cell receptor (TCR) elicits greater numbers of CD8 T cells but inferior antitumor responses. Our previous results suggested that programmed death 1 (PD-1) and its ligand (PD-L1) increased on antigen-specific CD8 T cells and tumor cells, respectively, after high-affinity vaccination. In this report, we use two murine models to investigate whether the dose, MHC affinity, or TCR affinity of an epitope affected the antitumor response via the PD-1/PD-L1 axis. T cells activated with high-affinity epitopes resulted in prolonged APC:T-cell contact time that led to elevated, persistent PD-1 expression, and expression of other checkpoint molecules, in vitro and in vivo Immunization with high-affinity epitopes also decreased antitumor efficacy in the absence of PD-1 blockade. Thus, APC:T-cell contact time can be altered by epitope affinity and lead to therapeutically relevant changes in vaccine efficacy mediated by changes in PD-1 expression. These findings have implications for the use of agents targeting PD-1 expression or function whenever high-affinity CD8 T cells are elicited or supplied by means of vaccination or adoptive transfer. Cancer Immunol Res; 5(8); 630-41. ©2017 AACR .<br /> (©2017 American Association for Cancer Research.)
- Subjects :
- Adoptive Transfer
Animals
B7-H1 Antigen genetics
CD8-Positive T-Lymphocytes immunology
Cancer Vaccines therapeutic use
Gene Expression Regulation, Neoplastic
Humans
Major Histocompatibility Complex immunology
Mice
Neoplasms genetics
Neoplasms immunology
Programmed Cell Death 1 Receptor genetics
Receptors, Antigen, T-Cell immunology
Vaccination methods
B7-H1 Antigen immunology
Cancer Vaccines immunology
Epitopes immunology
Neoplasms therapy
Programmed Cell Death 1 Receptor immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2326-6074
- Volume :
- 5
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer immunology research
- Publication Type :
- Academic Journal
- Accession number :
- 28634215
- Full Text :
- https://doi.org/10.1158/2326-6066.CIR-16-0374