Immunotherapy has transformed cancer therapy and positively impacted the lives of many patients. However, despite these advances, there remain barriers to the success of immunotherapy, and a majority of patients do not get better from immunotherapy. Unfortunately, soft tissue sarcomas are among the cancers which do not respond well to current immunotherapies, and the survival rate for these rare and difficult-to-treat cancers has barely improved for many years. Therefore, more research is needed to extend the benefits of immunotherapy to sarcoma patients.
The past decade has witnessed a big increase in research on natural killer (NK) cells. NK cells are a part of the immune system and are able to rapidly attack bacteria and cancer cells. Despite their ability to kill tumor cells, success with NK cells in cancer patients has hit roadblocks, in part because these cells lose killing capacity quickly, likely so the body can control them. This proposal seeks to understand how this exhaustion of NK cells can be overcome to better fulfill the promise of NK immunotherapy. We will block a novel receptor (TIGIT) on NK cells since this receptor is consistently upregulated on NK cells. We will use a diverse approach, including mice and human sarcoma samples. Then, we will pilot our new immunotherapy approach using NK cells and TIGIT blockade to release the brakes in a first-in-dog clinical trial for dog patients with soft tissue sarcomas. Cancer is a leading cause of death in dogs, as it is for humans.