T Cell Infiltration of the Prostate Induced by Androgen Withdrawal in Patients with Prostate Cancer

Manipulations capable of breaking host tolerance to induce tissue-specific T cell-mediated inflammation are of central importance to tumor immunotherapy and our understanding of autoimmunity. We demonstrate that androgen ablative therapy induces profuse T cell infiltration of benign glands and tumor...

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Bibliographic Details
Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 25; pp. 14565 - 14570
Main Authors:	Mercader, Maria, Bodner, Barbara K., Moser, Micheal T., Kwon, Pamela S., Eugene S. Y. Park, Manecke, Ryan G., Ellis, Thomas M., Wojcik, Eva M., Yang, Damu, Flanigan, Robert C., Waters, W. Bedford, Kast, W. Martin, Kwon, Eugene D.
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 04-12-2001 National Acad Sciences The National Academy of Sciences
Subjects:	Androgen Antagonists - therapeutic use Androgens Antigen-Presenting Cells - drug effects Antigen-Presenting Cells - immunology Antigen-Presenting Cells - pathology Antineoplastic Agents, Hormonal - therapeutic use Biological Sciences Blood Breast Neoplasms - drug therapy Breast Neoplasms - immunology CD4 antigen CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - pathology CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - pathology Cells Female Flutamide - therapeutic use Gene Rearrangement, beta-Chain T-Cell Antigen Receptor - drug effects Hormones Humans Immunology Lymphocyte Activation - drug effects Lymphocytes, Tumor-Infiltrating - drug effects Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - pathology Male Neoplasms, Hormone-Dependent - drug therapy Neoplasms, Hormone-Dependent - genetics Neoplasms, Hormone-Dependent - immunology Neoplasms, Hormone-Dependent - pathology Prospective Studies Prostate Prostate cancer Prostate gland Prostatic Neoplasms - drug therapy Prostatic Neoplasms - genetics Prostatic Neoplasms - immunology Prostatic Neoplasms - pathology Specimens Spectroscopic analysis Studies T cell antigen receptors T lymphocytes T-Lymphocytes - drug effects T-Lymphocytes - immunology T-Lymphocytes - pathology Tumors
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Summary:	Manipulations capable of breaking host tolerance to induce tissue-specific T cell-mediated inflammation are of central importance to tumor immunotherapy and our understanding of autoimmunity. We demonstrate that androgen ablative therapy induces profuse T cell infiltration of benign glands and tumors in human prostates. T cell infiltration is readily apparent after 7-28 days of therapy and is comprised predominantly of a response by CD4+ T cells and comparatively fewer CD8+ T cells. Also, T cells within the treated prostate exhibit restricted TCR V β gene usage, consistent with a local oligoclonal response. Recruitment/activation of antigen-presenting cells in treated prostate tissues may contribute to local T cell activation. The induction of T cell infiltration in prostate tissues treated with androgen ablation may have implications for the immunotherapeutic treatment of prostate cancer as well as other hormone-sensitive malignancies, including breast carcinoma.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-News-3 To whom reprint requests should be addressed at: Department of Urology/Cancer Immunology, Room 202 Cardinal Bernardin Cancer Center, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153. Edited by James P. Allison, University of California, Berkeley, CA, and approved October 8, 2001
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.251140998