T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer

Maria Mercader; Barbara K. Bodner; Micheal T. Moser; Pamela S. Kwon; Eugene S.Y. Park; Ryan G. Manecke; Thomas M. Ellis; Eva M. Wojcik; Damu Yang; Robert C. Flanigan; W. Bedford Waters; W. Martin Kast; Eugene D. Kwon

doi:10.1073/pnas.251140998

T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer

Maria Mercader, Barbara K. Bodner, Micheal T. Moser, Pamela S. Kwon, Eugene S.Y. Park, Ryan G. Manecke, Thomas M. Ellis, Eva M. Wojcik, Damu Yang, Robert C. Flanigan, W. Bedford Waters, W. Martin Kast, Eugene D. Kwon

Urology

Research output: Contribution to journal › Article › peer-review

285 Scopus citations

Abstract

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 Vβ 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.

Original language	English (US)
Pages (from-to)	14565-14570
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	98
Issue number	25
DOIs	https://doi.org/10.1073/pnas.251140998
State	Published - Dec 4 2001

Keywords

Adenocarcinoma of the prostate
Antigen-presenting cell
CD4+ and/or CD8+ T cell
Cytotoxic T cell
Hormone therapy

ASJC Scopus subject areas

General

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10.1073/pnas.251140998

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Mercader, M., Bodner, B. K., Moser, M. T., Kwon, P. S., Park, E. S. Y., Manecke, R. G., Ellis, T. M., Wojcik, E. M., Yang, D., Flanigan, R. C., Waters, W. B., Kast, W. M., & Kwon, E. D. (2001). T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer. Proceedings of the National Academy of Sciences of the United States of America, 98(25), 14565-14570. https://doi.org/10.1073/pnas.251140998

Mercader, M, Bodner, BK, Moser, MT, Kwon, PS, Park, ESY, Manecke, RG, Ellis, TM, Wojcik, EM, Yang, D, Flanigan, RC, Waters, WB, Kast, WM & Kwon, ED 2001, 'T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer', Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 25, pp. 14565-14570. https://doi.org/10.1073/pnas.251140998

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abstract = "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 Vβ 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.",

keywords = "Adenocarcinoma of the prostate, Antigen-presenting cell, CD4+ and/or CD8+ T cell, Cytotoxic T cell, Hormone therapy",

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AU - Park, Eugene S.Y.

AU - Manecke, Ryan G.

AU - Ellis, Thomas M.

AU - Wojcik, Eva M.

AU - Yang, Damu

AU - Flanigan, Robert C.

AU - Waters, W. Bedford

AU - Kast, W. Martin

AU - Kwon, Eugene D.

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AB - 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 Vβ 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.

KW - Adenocarcinoma of the prostate

KW - Antigen-presenting cell

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KW - Cytotoxic T cell

KW - Hormone therapy

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T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer

Abstract

Keywords

ASJC Scopus subject areas

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