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(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.
Zimmermann
Valérie S
VS
Cancer Immunotherapy and Gene Therapy Program, Department of Biotechnology, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
Casati
Anna
A
Schiering
Chris
C
Caserta
Stefano
S
Hess Michelini
Rodrigo
R
Basso
Veronica
V
Mondino
Anna
A
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D039481:CD11b Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000276:immunology; D009369:Neoplasms / Q000517:prevention & control* / Q000628:therapy; D010455:Peptides / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology*; D019707:Receptors, Chemokine / Q000032:analysis; D014611:Vaccination / Q000379:methods*
D000953:Antigens, Protozoan; D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D015800:Protozoan Proteins; D019707:Receptors, Chemokine; C093139:LACK antigen, Leishmania