Decoding a role for a natural killer cell-based immunotherapy in high-grade serous carcinoma within an engineered tumor microenvironment

High-grade serous carcinoma (HGSC) is the deadliest form of ovarian cancer. It is often not diagnosed until it has grown a lot, and this can mean that treatment often fails, or tumors grow back. The current standard treatments -chemotherapy and surgery - do not cure the majority of patients. Unfortunately, there haven't been many advances in treatments for HGSC in the past 30 years. One of newest treatments for cancer that has shown good success is called immunotherapy, which targets the patient's own immune cells, and encourages them to attack and clear the tumor. This seemed promising for use in HGSC, but unfortunately, success has been low. There is a type of immunotherapy that might be useful in the fight against HGSC: natural killer (NK) cells. We know from research that patients with NK cells in their tumors have longer survival, but we do not yet understand what allows NK cells to enter a tumor and kill it. An additional challenge in cancer drug development is that current research models are not often representative of an actual tumor, so results in these models don't often match up when they move on to clinical trials. Mouse models can be helpful, but it is hard to do quick and mechanistic studies with them. In place of existing models, I have already developed an in vitro 3-D model of HGSC. In my PhD studies, I will model different HGSC tumor scenarios and attempt to treat them with different combinations and sequences of therapies, including existing and new (NK cell-based) therapeutics. With this, I hope to improve outcomes for HGSC patients by identifying more personalized approaches based on tumor profiles and identify a role for NK cells as a new therapeutic.