Seth B. Coffelt, PhD, CLIP Investigator University of Glasgow Area of Research: Liver Cancer Hepatocellular carcinoma (HCC) is fourth largest cause of cancer-related deaths worldwide. T cell checkpoint inhibitors are approved for HCC and these drugs show some clinical benefit. However, long-term, durable responses after cancer immunotherapy are lacking in most patients with HCC. Using a new genetically engineered mouse model of HCC driven by mutant beta-catenin and overexpression of the Myc oncogene, Dr. Coffelt’s team found that gd T cells promote liver cancer progression. The overall goal of his new research is to dissect the role of gd T cells in HCC progression and determine whether they are appropriate candidates for cancer immunotherapy. He hypothesizes that cancerous hepatocytes educate gd T cells to assist in tumor progression and that targeting these cells in combination with standard-of-care will extend survival. This hypothesis will be tested in the following specific aims: Aim 1) Determine whether anti-cancer therapy synergizes with gd T cell immunotherapy; Aim 2) Perform in depth characterization of HCC-associated mouse and human gd T cells; and Aim 3) Determine the mechanism by which gd T cells promote HCC. The data generated from this project will provide valuable insights into an understudied cancer type and an understudied immune cell subset, by focusing on gd T cell-mediated HCC progression. These findings have the potential to uncover new targets for cancer immunotherapy. Projects and Grants Investigating gamma delta T cells in hepatocellular carcinoma for immunotherapy University of Glasgow | Liver Cancer | 2021
