Our group has shown that natural killer cells can be injected into patients as a treatment for cancer. We are now studying what happens when these cells become overstimulated and dysfunctional, a process known as exhaustion. We have developed a novel model of natural killer cell exhaustion to identify the cellular mechanisms that control this process. Our goal is to develop new methods of enhancing their function, such that therapeutic natural killer cells resist exhaustion and eradicate tumors more effectively.

Solid tumors have abnormal blood vessels and high energy demands which means oxygen is often scarce. Tumor cells are adapted to this environment, but natural killer cells entering this environment from the blood are not. We are studying how low oxygen impacts the ability of natural killer cells to kill tumor cells to determine how to make the function better in oxygen-limited environments.

Not all immune cells fight against the tumor. Some support the tumor and prevent other immune cells from attacking the tumor. These are known as suppressive cells and include types of T cells (regulatory T cells) and myeloid cells (tumor-associated macrophages and myeloid-derived suppressor cells). We are investigating how these cells interact with natural killer cells and whether we can alter or destroy these suppressive cells through the design of therapeutic cells and biologics.

Natural killer cells are present as a population in the blood and as a smaller fraction of the cells found within organs. One of the challenges of natural killer cell-focused therapies is ensuring they are delivered effectively into the tumor in order to kill tumor cells and recruit other immune cells. We are experimenting with different routes of delivery and designing means to recruit these cells efficiently into the tumor.