This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Degl'Innocenti, E. Articles by Bellone, M. Search for Related Content PubMed PubMed Citation Articles by Degl'Innocenti, E. Articles by Bellone, M.

Peripheral T-Cell Tolerance Associated with Prostate Cancer Is Independent from CD4⁺CD25⁺ Regulatory T Cells

¹ Cancer Immunotherapy and Gene Therapy Program and ² Unità Operativa Anatomia Patologica, Istituto Scientifico San Raffaele, Milan, Italy

Requests for reprints: Matteo Bellone, Laboratory of Cellular Immunology, Cancer Immunotherapy and Gene Therapy Program, 3P-A1, Dibit, Istituto Scientifico San Raffaele, Via Olgettina 58, 20132, Milan, Italy. Phone: 39-02-2643-4789; Fax: 39-02-2643-4786; E-mail: bellone.matteo{at}hsr.it.

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- 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]

This article has been cited by other articles:

				M. A. de Witte, G. M. Bendle, M. D. van den Boom, M. Coccoris, T. D. Schell, S. S. Tevethia, H. van Tinteren, E. M. Mesman, J.-Y. Song, and T. N. M. Schumacher TCR Gene Therapy of Spontaneous Prostate Carcinoma Requires In Vivo T Cell Activation J. Immunol., August 15, 2008; 181(4): 2563 - 2571. [Abstract] [Full Text] [PDF]