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

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.