Gamma-Delta T-Cells Regulate Pancreatic Tumorigenesis

• Applicant: Privatdozentin Dr. Lena Seifert
• Subject Area: General and Visceral Surgery
• Term: from 2014 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 259369076

Pancreatic ductal adenocarcinoma is a highly aggressive tumor, which carries a poor prognosis. Studies investigating the pathogenesis of pancreatic ductal adenocarcinoma have primarily focused on the molecular biology of pancreatic tumor cells themselves. However, more recent work suggests that the contribution of the surrounding pancreatic tumor stroma, composed of inflammatory cells and fibrous tissue. Gamma-delta T cells are a distinct T cell subset closely aligned with the innate immune system whose role in cancer biology is emerging in diverse malignancies such as melanoma and breast cancer. However, intra-pancreatic gamma-delta T cells have never been described. We found that a novel small population of gamma-delta T cells infiltrates the injured pre-neoplastic pancreas and early pancreatic cancer in mice and humans. This population exhibits a highly activated phenotype and is distinct from gamma-delta T cells found in other compartments. We also found that the pancreatic tumor microenvironment is rife with activating ligands for gamma-delta T cells. Further, our preliminary work suggested that gamma-delta T cell deletion markedly exacerbated pancreatic inflammation and led to the expansion of tumor-promoting Th2 cells. Based on these observations, we postulate that tumor infiltrating gamma-delta T cells protect against pancreatic cancer progression by directly inducing cytotoxic effects on transformed epithelial cells and by limiting expansion and Th2 deviation of CD4 T cells.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. George Miller