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SP1 Overcoming T cell exhaustion in PDAC: NLRP3 inflammasome-dependent effects on T cell function in pancreatic carcinoma

PD Dr. Christian Bauer

Prof. Magdalena Huber

Project SP1 investigates T cell subpopulations in pancreatic cancer with a focus on the role of NLRP3 and NLRP3-dependent cytokines IL-1beta and IL-18. Based on our previous finding of IL-18R signaling-induced T cell exhaustion of intratumoral cytotoxic T cells (CTLs), the molecular mechanisms of NLRP3-mediated T cell dysfunction will be further elucidated. This will include analysis of the transcriptional and epigenetic patterns associated with IL-18R signaling by RNA-Seq and ATAC-Seq, as well as establishing advanced models of T cells cytotoxicity such as a murine CAR T cell model. In a second part, the role of Tc17 T cells in pancreatic carcinoma will be investigated, in particular crosstalk between Tc17 cell, inflammatory cancer-associated fibroblasts (iCAFs) and tumor cells. We will focus on changes in the transcriptional landscape of pancreatic cancer cells induced by iCAFs. As a third objective, findings on IL-18R signaling and Tc17 cells in pancreatic carcinoma will be transferred to human sample material in cooperation with Z-Biobank. In cooperation with Z-Imaging, interaction of Tc17 cells and CTLs with target cells will be visualized, and the influence of iCAFs will be investigated.