Zoe Schmiechen was awarded an NIH F31 through the National Cancer Institute (NCI). Zoe is a MICaB predoctoral student in Ingunn Stromnes’ lab. Zoe's grant is entitled "Elucidating the Role of Tregs in Cancer Metastasis and T Cell Dysfunction".  Pancreatic ductal adenocarcinoma (PDA) is the 4th leading cause of cancer-related deaths and has a dismal 5-year survival rate of 10%. Lethality is attributed to early metastasis, late detection, and therapeutic resistance. Cytotoxic CD8 T cells are the principal mediators of immune surveillance and are critical for cancer eradication. However, in PDA and other cancers, CD8 T cells progressively lose their cytotoxic function, and are thus characterized as exhausted. Immune checkpoint blockade aims to correct T cell exhaustion by blocking inhibitory signaling and has revolutionized the treatment of many malignancies. However, PDA is largely resistant. As such, this grant will seek to understand the mechanisms driving CD8 T cell exhaustion in Pancreatic ductal adenocarcinoma (PDA) and how PDA evades activated immune response after immunotherapy treatment. Additionally, this grant will study cancer cell-intrinsic and -extrinsic mechanisms of PDA metastasis and will test the central hypothesis that immunotherapy selects for metastatic cancer cells that promote intratumoral Tregs that cause CD8 T cell dysfunction. Completion of the proposed research strategy will reveal mechanisms of metastasis and CD8 T cell dysfunction in PDA and identify a therapeutic target(s) in the hope of reducing PDA lethality.