Conversion of tumor-specific CD4+ T-cell tolerance to T-cell priming through in vivo ligation of CD40.
Tumor antigen-specific T-cell tolerance limits the efficacy of therapeutic cancer vaccines. Antigen-presenting cells mediate the induction of T-cell tolerance to self-antigens. We therefore assessed the fate of tumor-specific CD4+ T cells in tumor-bearing recipients after in vivo activation of antigen-presenting cells with antibodies against CD40. Such treatment not only preserved the responsiveness of this population, but resulted in their endogenous activation. Established tumors regressed in vaccinated mice treated with antibody against CD40 at a time when no response was achieved with vaccination alone. These results indicate that modulation of antigen-presenting cells may be a useful strategy for enhancing responsiveness to immunization.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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Sotomayor
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Borrello
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Tubb
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Rattis
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Bien
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Lu
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Fein
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Schoenberger
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Levitsky
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D019496:Cancer Vaccines; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance; D007680:Kidney Neoplasms / Q000276:immunology / Q000517:prevention & control*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D017710:Lymphocyte Transfusion; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D014407:Tumor Cells, Cultured
D019013:CD40 Antigens; D019496:Cancer Vaccines; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D023201:CD40 Ligand