Abeloff V Scholar * (Tie for Top Rank)
The treatments for head and neck cancers have been revolutionized by the development of immunotherapies. However, many treated cancer patients often experience relapse. Without a clear understanding of why and how cancer cells resists and relapses after current immunotherapy treatment, it is impossible to design a better immunotherapy, and the current treatments for cancer patients eventually fail due to relapse. For advancing clinical outcomes of future treatments, the goal of this proposal is to identify key mechanisms driving cancer relapse from immunotherapy. Recently, we discovered a special group of tumor cells that resemble the stem cells responsible for regenerating normal tissues. Importantly, these tumor cells appear to be the major survivor of immunotherapy treatment and the cause of tumor relapse. This key finding raised the possibility of targeting the critical molecular programs driving the unique immune resistance of these special cancer cells to prevent cancer relapse. In this study we will develop a new immune-oncology platform for head and neck cancer, so we can achieve rapid genetic manipulation of cancer cells directly in live mice. With this powerful approach we aim to identify the stem cells-specific factors that govern both intrinsic and extrinsic immune resistance mechanisms in head and neck cancer. The information derived from this study will pave the way to the development of the next generation of immunotherapy for head and neck cancers with the capacity to overcome relapse.