Tumors hamper the immunogenic competence of CD4+ T cell-directed dendritic cell vaccination

Zimmermann, Valérie S, Casati, Anna, Schiering, Chris, Caserta, Stefano, Hess Michelini, Rodrigo, Basso, Veronica and Mondino, Anna (2007) Tumors hamper the immunogenic competence of CD4+ T cell-directed dendritic cell vaccination. Journal of Immunology, 179 (5). pp. 2899-2909. ISSN 0022-1767

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Dendritic cells loaded with tumor-derived peptides induce protective CTL responses and are under evaluation in clinical trails. We report in this study that prophylactic administration of dendritic cells loaded with a MHC class II-restricted peptide derived from a model tumor Ag (Leishmania receptor for activated C kinase (LACK)) confers protection against LACK-expressing TS/A tumors, whereas therapeutic vaccination fails to cure tumor-bearing mice. Although CD4+ T cell-directed dendritic cell vaccination primed effector-like (CD44(high)CD62L(low), IL-2(+), IFN-gamma(+)) and central memory-like lymphocytes (CD44(high)CD62L(high), only IL-2(+)) in tumor-free mice, this was not the case in tumor-bearing animals in which both priming and persistence of CD4+ T cell memory were suppressed. Suppression was specific for the tumor-associated Ag LACK, and did not depend on CD25+ T cells. Because T cell help is needed for protective immunity, we speculate that the ability of tumors to limit vaccine-induced CD4+ T cell memory could provide a partial explanation for the limited efficacy of current strategies.

Item Type: Article
Keywords: dendritic cells; tumour immunology; vaccination; T cell responses
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Brighton and Sussex Medical School > Global Health and Infection
Subjects: Q Science > QR Microbiology > QR0180 Immunology
R Medicine > RM Therapeutics. Pharmacology > RM0270 Immunotherapy. Serotherapy
Depositing User: Stefano Caserta
Date Deposited: 30 Sep 2015 07:02
Last Modified: 21 Sep 2017 13:56
URI: http://srodev.sussex.ac.uk/id/eprint/56879
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