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Endocrine and Oncologic Surgery Research Lab
Harrison Department of Surgical Research
Brian J. Czerniecki, M.D., Ph.D.
Assessing the Role of IL-17 Immune Response
in Breast Cancer Development
Our laboratory has a long standing history of studies on the biology of dendritic cell activation. We were one of the first groups to demonstrate that IL-12 production by DC enhanced the functional avidity of anti-tumor CD8+ T cells Xu et. al J. Immunology 2003. We have demonstrated that toll like receptors either dual (TLR) agonists or combinations of interferon gamma and TLR agonists induced high levels of IL-12 by DC and were generated for the clinical trials utilized above Xu et. al Surgery 140:170-8, 2006. More recently we demonstrated that single TLR agonist do not induce IL-12 production by DC but rather IL-23 and promote Th17 responses as opposed to Th1 (Roses J. Immunology 181:5120-27 2008). Hence DC environmental signals determine whether Th17 or Th1 responses can dominate an immune response. We have shown now and submitted a manuscript demonstrating prostaglandin E2 (PGE2) can steer DC activation toward IL-23 production while inhibiting IL-12 production (submitted for publication). IL-17 is associated with pro-angiogenesis, and chronic inflammation and tumor promotion and with chronic inflammation being associated with breast cancer development we hypothesize that PGE2 produced in the breast cancer stroma would steer a Th17 response and promote breast cancer development. We have shown that Th17 cells are prominently found surrounding ducts in DCIS and early invasive breast cancer (submitted for publication) and are currently preparing to investigate the role Th17 cells play in the development of breast cancer and their role in treatment of breast cancer using murine breast tumor models.


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