Volunteer Grant funded by the V Foundation Wine Celebration in honor of Robert and Gail Sims
The advent of immunotherapy has dramatically changed the landscape of cancer treatments. The power of immunotherapy its potential to induce long-lasting benefits for terminally ill patients, however only a minority of patients are currently responding to the treatment. We have previously shown that the composition of the immune cells found within the tumor is critically important for the therapeutic outcome, with two immune cell types being required for a strong and effective tumor elimination. These cell types are so-called killer T-cells, which recognize and eliminate tumor cells and dendritic cells, which are needed to “license” T cells to kill.
Killer T-cells are most effective when they are directed against targets only present on tumor cells and when all tumor cells have an evenly distributed expression of this target. However, in most tumors the targets are unevenly represented and only partially present representing a hurdle for successful tumor cell elimination. But more importantly this diffuse pattern directly weakens the strength of the killer T-cell response and changes the composition of immune cells in the tumor. To date we do not understand why a weaker T-cell response is observed and how we could overcome this shortcoming therapeutically. In the funded study, we aim to understand the dynamics of a killer T-cell responses against tumors with uneven target expression. In doing so we aim to understand which factors impact the expansion and function of killer T-cells and ultimately harness this knowledge to expand the fraction of patients benefiting from immunotherapy.