Mercader M, Bodner B K, Moser M T, Kwon P S, Park E S, Manecke R G, Ellis T M, Wojcik E M, Yang D, Flanigan R C, Waters W B, Kast W M, Kwon E D
Department of Urology, Loyola University of Chicago, Maywood, IL 60153, USA.
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14565-70. doi: 10.1073/pnas.251140998.
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.
能够打破宿主耐受性以诱导组织特异性T细胞介导的炎症的操作对于肿瘤免疫治疗以及我们对自身免疫的理解至关重要。我们证明雄激素剥夺疗法会诱导人前列腺中良性腺体和肿瘤出现大量T细胞浸润。治疗7 - 28天后,T细胞浸润很明显,主要由CD4 + T细胞反应组成,CD8 + T细胞相对较少。此外,经治疗的前列腺内的T细胞表现出受限的TCR Vβ基因使用情况,这与局部寡克隆反应一致。治疗前列腺组织中抗原呈递细胞的募集/激活可能有助于局部T细胞激活。雄激素剥夺治疗的前列腺组织中T细胞浸润的诱导可能对前列腺癌以及其他激素敏感性恶性肿瘤(包括乳腺癌)的免疫治疗具有意义。