Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Ovarian cancer (OC) is the leading cause of cancer death arising from the female reproductive system. Most women are diagnosed after the cancer has spread across the abdomen, limiting available treatment options. The OC is allowed to grow in part because the immune system in the abdomen becomes ineffective at killing the cancer. Our research will address this issue by asking why the immune cells in our abdomen stop working in OC, and how we can reactivate them to destroy the tumours. Studying mice with OC, we found that a specific immune-suppressing cell in the abdomen increased 40-fold. The immune suppression was caused by the cell producing a molecule that activates an "off switch" when it encounters working immune cells. When we put a drug that blocks this molecule into the blood, we found that the treatment did not reach the abdomen, where the "off switch" was located. However, when we injected the therapy directly into the abdomen, the drug successfully reached its target, activated immune cells, and improved the survival time in mice with OC. Another approach we will test involves removing immune cells, modifying them to be more effective at cancer killing, and then returning them to the body. Despite successes in other cancers, this treatment is ineffective in OC. We will test whether these immune cells can successfully reach the abdomen and tumours if given by blood, or if they are better placed directly into the abdomen where the cancer is located. To support this, we developed a method using microscopes to see how these modified cells behave, specifically examining how many reach the tumour, where they are stopped, and why those that do arrive fail to kill the cancer. Together, our work on blocking immune "off switches" and the behaviour of modified immune cells will be combined into enhanced OC treatments that restore the immune system's ability to attack cancer and overcome the barriers that prevent it from doing so.