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

Zimmermann, V. S.; Casati, A.; Schiering, C.; Caserta, S.; Hess Michelini, R.; Basso, V.; Mondino, A.

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 high CD62L low , IL-2 + , IFN-γ + ) 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.

Citation

Zimmermann, V. S., Casati, A., Schiering, C., Caserta, S., Hess Michelini, R., Basso, V., & Mondino, A. (2007). Tumors hamper the immunogenic competence of CD4+T cell-directed dendritic cell vaccination. Journal of Immunology, 179(5), 2899-2909. https://doi.org/10.4049/jimmunol.179.5.2899

• Journal Article Type: Article
• Acceptance Date: Jun 21, 2007
• Online Publication Date: Aug 20, 2007
• Publication Date: Sep 1, 2007
• Deposit Date: Jun 28, 2018
• Journal: Journal of Immunology
• Print ISSN: 0022-1767
• Electronic ISSN: 1550-6606
• Publisher: American Association of Immunologists
• Peer Reviewed: Peer Reviewed
• Volume: 179
• Issue: 5
• Pages: 2899-2909
• DOI: https://doi.org/10.4049/jimmunol.179.5.2899
• Public URL: https://hull-repository.worktribe.com/output/620585
• Publisher URL: http://www.jimmunol.org/content/179/5/2899