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CD4+ lymphocytes modulate prostate cancer progression in mice
Author(s) -
Poutahidis Theofilos,
Rao Varada P.,
Olipitz Werner,
Taylor Christie L.,
Jackson Erin A.,
Levkovich Tatiana,
Lee Chung Wei,
Fox James G.,
Ge Zhongming,
Erdman Susan E.
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24452
Subject(s) - prostate cancer , proinflammatory cytokine , prostate , medicine , intraepithelial neoplasia , inflammation , cancer , immune system , il 2 receptor , cancer research , immunology , endocrinology , t cell
Chronic inflammation contributes to the development of prostate cancer in humans. Here, we show that male Apc Min /+ mice also develop prostate carcinoma with increasing age, mimicking that seen in humans in their 5th or 6th decade of life. Proinflammatory cytokines were significantly linked with cancer and increasing age in our mouse model; however, prostate and bowel tissues lacked evidence of inflammatory cell infiltrates other than mast cells. Lymphocytes protected against cancer, and protection from prostate cancer resided in antiinflammatory CD4 + CD25 + regulatory (T REG ) cells that downregulated inflammatory cytokines. Supplementation with syngeneic T REG cells collected from wild‐type mice reduced the levels of interleukin (IL)‐6 ( p < 0.05) and IL‐9 ( p < 0.001) and lowered prostate cancer risk ( p < 0.05). Depletion of CD25 + cells in 2‐month‐old animals increased the expression of IL‐6 ( p < 0.005) within prostate and increased the frequency of high‐grade prostatic intraepithelial neoplasia ( p < 0.05) and microinvasive prostatic carcinoma ( p < 0.05) in dorsolateral prostate. Depletion of CD25 + cells in young animals also increased the frequency of intestinal cancer in Min mice. Taken together, chronically elevated proinflammatory cytokines promoted carcinoma in Apc Min /+ mice. T REG lymphocytes downregulated inflammation‐associated carcinogenic processes and contributed to immune and epithelial homeostasis. © 2009 UICC