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 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 Vbeta 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.
Mercader
M
M
Department of Urology, Loyola University of Chicago, Maywood, IL 60153, USA.
Bodner
B K
BK
Moser
M T
MT
Kwon
P S
PS
Park
E S
ES
Manecke
R G
RG
Ellis
T M
TM
Wojcik
E M
EM
Yang
D
D
Flanigan
R C
RC
Waters
W B
WB
Kast
W M
WM
Kwon
E D
ED
D000726:Androgen Antagonists / Q000627:therapeutic use*; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D005485:Flutamide / Q000627:therapeutic use; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000187:drug effects; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D005485:Flutamide