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

Valérie S. Zimmermann, Anna Casati, Chris Schiering, Stefano Caserta, Rodrigo Hess Michelini, Veronica Basso, Anna Mondino

Research output: Contribution to journalArticlepeer-review

Abstract

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 highCD62L low, IL-2 +, IFN-γ +) and central memory-like lymphocytes (CD44 highCD62L 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.

Original languageEnglish
Pages (from-to)2899-2909
Number of pages11
JournalJournal of Immunology
Volume179
Issue number5
Publication statusPublished - Sep 1 2007

ASJC Scopus subject areas

  • Immunology

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