The role of intratumoral gamma-delta T cells in pancreatic cancer – characterization, interaction and modulation

• Applicant: Privatdozentin Dr. Lena Seifert
• Subject Area: General and Visceral Surgery
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437219199

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with a 5-year survival rate lower than 7%. PDAC is predicted to be the second most common cause of cancer-related death by the year 2030. Current treatment options are limited, but new immunotherapeutic strategies have shown promising results in a variety of gastrointestinal tumors. PDAC has a dense infiltrate of immune cells that participate in tumor development and progression. Tumor growth can be blocked or promoted through the interaction between tumor and immune cells. Gamma-delta T cells, a subpopulation of T cells without antigen-specific properties, can kill infected cells and produce important signals for the coordination of the immune response. We have previously shown that activated gamma-delta T cells infiltrate murine and human PDAC. In comparison to CD4+ and CD8+ T cells, gamma-delta T cells constitute the most common T cell population in PDAC. Furthermore, we demonstrated an impressive tumor-protective effect in KC;TCRδ–/–-mice. Based upon our previous findings we will determine the clinical relevance of gamma-delta T cells in human PDAC. Additionally, we will analyze the interaction and the reciprocal influence of gamma-delta T cells and other components oft he pancreatic tumor microenvironment. We will test the modulation of gamma-delta T cells in murine and human PDAC and thereby identify relevant therapeutic strategies. The aim of this project is to elucidate the cellular mechanisms of the interaction between gamma-delta T cells and other immune cells and PDAC. Results from this project will contribute to a detailed understanding of pancreatic tumor biology and ultimately lead to the development of new therapeutic concepts.

• DFG Programme: Research Grants