CD4+ lymphocytes modulate prostate cancer progression in mice
Theofilos Poutahidis
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Laboratory of Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
Search for more papers by this authorVarada P. Rao
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorWerner Olipitz
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorChristie L. Taylor
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorErin A. Jackson
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorTatiana Levkovich
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorChung Wei Lee
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorJames G. Fox
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorZhongming Ge
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorCorresponding Author
Susan E. Erdman
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Fax: +617-258-5708.
Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Ave., Bldg. 68-0032, Cambridge, MA 02139, USASearch for more papers by this authorTheofilos Poutahidis
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Laboratory of Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
Search for more papers by this authorVarada P. Rao
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorWerner Olipitz
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorChristie L. Taylor
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorErin A. Jackson
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorTatiana Levkovich
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorChung Wei Lee
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorJames G. Fox
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorZhongming Ge
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Search for more papers by this authorCorresponding Author
Susan E. Erdman
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA
Fax: +617-258-5708.
Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Ave., Bldg. 68-0032, Cambridge, MA 02139, USASearch for more papers by this authorAbstract
Chronic inflammation contributes to the development of prostate cancer in humans. Here, we show that male ApcMin/+ 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 (TREG) cells that downregulated inflammatory cytokines. Supplementation with syngeneic TREG 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 ApcMin/+ mice. TREG lymphocytes downregulated inflammation-associated carcinogenic processes and contributed to immune and epithelial homeostasis. © 2009 UICC
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