Antigen Specific T-Cell Responses Against Tumor Antigens are Controlled by Regulatory T Cells in Patients With Prostate Cancer
- 30 April 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of Urology
- Vol. 187 (4), 1458-1465
- https://doi.org/10.1016/j.juro.2011.11.083
Abstract
Purpose: Immunotherapy is a promising approach in an effort to control castration resistant prostate cancer. We characterized tumor antigen reactive T cells in patients with prostate cancer and analyzed the suppression of antitumor responses by regulatory T cells. Materials and Methods: Peripheral blood samples were collected from 57 patients with histologically confirmed prostate cancer, 8 patients with benign prostatic hyperplasia and 16 healthy donors. Peripheral blood mononuclear cells were isolated and antigen specific interferon-gamma secretion of isolated T cells was analyzed by enzyme-linked immunospot assay. T cells were functionally characterized and T-cell responses before and after regulatory T-cell depletion were compared. As test tumor antigens, a panel of 11 long synthetic peptides derived from a total of 8 tumor antigens was used, including prostate specific antigen and prostatic acid phosphatase. Results: In patients with prostate cancer we noted a 74.5% effector T-cell response rate compared with only 25% in patients with benign prostatic hyperplasia and 31% in healthy donors. In most patients 2 or 3 tumor antigens were recognized. Comparing various disease stages there was a clear increase in the immune response against prostate specific antigens from intermediate to high risk tumors and castration resistant disease. Regulatory T-cell depletion led to a significant boost in effector T-cell responses against prostate specific antigen and prostatic acid phosphatase. Conclusions: Tumor specific effector T cells were detected in most patients with prostate cancer, especially those with castration resistant prostate cancer. Since effector T-cell responses against prostate specific antigens strongly increased after regulatory T-cell depletion, our results indicate that immunotherapy efficacy could be enhanced by decreasing regulatory T cells.Keywords
This publication has 30 references indexed in Scilit:
- Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre- versus post-vaccinationCancer Immunology, Immunotherapy, 2010
- Prostate cancer as a model for tumour immunotherapyNature Reviews Immunology, 2010
- Sipuleucel-T Immunotherapy for Castration-Resistant Prostate CancerNew England Journal of Medicine, 2010
- In situ Vaccination Combined with Androgen Ablation and Regulatory T-Cell Depletion Reduces Castration-Resistant Tumor Burden in Prostate-Specific Pten Knockout MiceCancer Research, 2010
- Androgen ablation augments human HLA2.1‐restricted T cell responses to PSA self‐antigen in transgenic miceThe Prostate, 2010
- Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in Metastatic Castration-Resistant Prostate CancerJournal of Clinical Oncology, 2010
- Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinomaJCI Insight, 2009
- Autoantibodies to tumor‐associated antigens: reporters from the immune systemImmunological Reviews, 2008
- Reversal of Tumor-Mediated ImmunosuppressionClinical Cancer Research, 2007
- Effect of Adenovirus-Mediated Heat Shock Protein Expression and Oncolysis in Combination with Low-Dose Cyclophosphamide Treatment on Antitumor Immune ResponsesCancer Research, 2006