title: CD4+ T cells are able to promote tumor growth through inhibition of tumor-specific CD8+ T-cell responses in tumor-bearing hosts.
abstract: Modulation of the immune response by established tumors may contribute to the limited success of therapeutic vaccination for the treatment of cancer compared with vaccination in a preventive setting. We analyzed the contribution of the CD4+ T-cell population to the induction or suppression of tumor-specific CD8+ T cells in a tumor model in which eradication of tumors crucially depends on CD8+ T cell-mediated immunity. Vaccine-mediated induction of protective antitumor immunity in the preventive setting (i.e., before tumor challenge) was CD4+ T cell dependent because depletion of this T-cell subset prevented CD8+ T-cell induction. In contrast, depletion of CD4+ cells in mice bearing established E1A+ tumors empowered the mice to raise strong CD8+ T-cell immunity capable of tumor eradication without the need for tumor-specific vaccination. Spontaneous eradication of tumors, which had initially grown out, was similarly observed in MHC class II-deficient mice, supporting the notion that the tumor-bearing mice harbor a class II MHC-restricted CD4+ T-cell subset capable of suppressing a tumor-specific CD8+ T-cell immune response. The deleterious effects of the presence of CD4+ T cells in tumor-bearing hosts could be overcome by CD40-triggering or injection of CpG. Together these results show that CD4+ T cells with a suppressive activity are rapidly induced following tumor development and that their suppressive effect can be overcome by agents that activate professional antigen-presenting cells. These observations are important for the development of immune interventions aiming at treatment of cancer.
authors.affiliation: Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Annemieke Th
authors.initials: AT
authors.lastname: den Boer
authors.forename: Geertje J D
authors.initials: GJ
authors.lastname: van Mierlo
authors.forename: Marieke F
authors.initials: MF
authors.lastname: Fransen
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Rienk
authors.initials: R
authors.lastname: Offringa
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D048708:Cell Growth Processes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D015375:Receptors, Interleukin-2