Peripheral T-cell tolerance associated with prostate cancer is independent from CD4(+)CD25(+) regulatory T cells
| Autor: | Matteo Grioni, Claudio Doglioni, Maria Teresa Sabrina Bertilaccio, Rodrigo Hess-Michelini, Elena Degl'Innocenti, Massimo Freschi, Giusy Capuano, Matteo Bellone, Elena Jachetti |
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| Přispěvatelé: | Degl'Innocenti, Elena, Grioni, Matteo, Capuano, Giusy, Jachetti, Elena, Freschi, Massimo, Bertilaccio Maria, T. S., Hess Michelini, Rodrigo, Doglioni, Claudio, Bellone, Matteo |
| Rok vydání: | 2008 |
| Předmět: |
Male
Aging Cancer Research T cell Mice Transgenic chemical and pharmacologic phenomena Adenocarcinoma T-Lymphocytes Regulatory Lymphocyte Depletion Immune tolerance Mice Immune system Immune Tolerance Animals Medicine IL-2 receptor business.industry Vaccination Interleukin-2 Receptor alpha Subunit Antibodies Monoclonal Prostatic Neoplasms FOXP3 Forkhead Transcription Factors Dendritic Cells Dendritic cell Mice Mutant Strains Tolerance induction medicine.anatomical_structure Oncology CD4 Antigens Immunology Lymph Nodes business Tramp |
| Popis: | CD4+CD25+Foxp3+ regulatory T cells (Treg) are thought to suppress the natural and vaccine-induced immune response against tumor-associated antigens (TAA). Here, we show that Treg accumulate in tumors and tumor-draining lymph nodes of aging transgenic adenocarcinoma of the mouse prostate (TRAMP) male mice, which spontaneously develop prostate cancer. TAA overexpression and disease progression associate also with induction of TAA-specific tolerance. TAA-specific T cells were found in the lymphoid organs of tumor-bearing mice. However, they had lost the ability to release IFN-γ and kill relevant targets. Neither in vivo depletion of Treg by PC61 monoclonal antibody followed by repeated vaccinations with antigen-pulsed dendritic cells nor the combined treatment with 1-methyl-l-tryptophan inhibitor of the enzyme indoleamine 2,3-dyoxigenase, PC61 antibody, and dendritic cell vaccination restored the TAA-specific immune response. Treg did not seem to control the early phases of tolerance induction, as well. Indeed, depletion of Treg, starting at week 6, the age at which TRAMP mice are not yet tolerant, and prolonged up to week 12, did not avoid tolerance induction. A similar accumulation of Treg was found in the lymph nodes draining the site of dendritic cell vaccination both in TRAMP and wild-type animals. Hence, we conclude that Treg accrual is a phenomenon common to the sites of an ongoing immune response, and in TRAMP mice in particular, Treg are dispensable for induction of tumor-specific tolerance. [Cancer Res 2008;68(1):292–300] |
| Databáze: | OpenAIRE |
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