Pancreatic cancer is the deadliest type of cancer due to its invasive and fast metastasizing nature. In various pancreatic cancer mouse and rat models, our group could show that blocking of CD44v6, a member of the CD44 family of transmembrane proteins with species-specific peptides, not only on human cancer cells (L3.6pl) but also on endogenous murine (host) cells, led to reduction of tumor volume and metastatic burden. We are currently investigating the role of CD44 on cancer-associated fibroblasts (CAFs) that likely influence tumor progression by interactions with other stromal cells and cancer cells.  Preliminary results in cancer-associated fibroblasts show that the knockout of CD44 leads to their inactivation, reflected in decreased marker expression, and altered morphology. CAFs constitute a heterogenous cell population including myofibroblastic (myCAFs) and inflammatory CAFs (iCAFs), playing roles in immunosuppression and fibrosis, which are crucial for tumor progression. Especially regarding the widely emerging field of immunotherapies in pancreatic cancer, understanding the modulation of antigen-presenting cells and T cell response by iCAFs is of great interest. Until now we could identify that the deactivation of the CAFs through the knockout of CD44 influences their inhibitory effect on dendritic cells, resulting in a decreased expression of immunosuppressive cytokines. To investigate the role of Cd44 in the whole CAF population in vivo, we have removed Cd44 by means of Cd44fl/fl;PDGFRβCreERT2 mice and are examining the consequences of the absence of all CD44 isoforms in CAFs on tumor growth, tumor composition, immune escape and metastasis.