Mitochondrial Stress Impairs Protective T Cell Immunity in Ovarian Cancer

Project summary

Treatment options remain limited for women with ovarian cancer as they usually do not respond well to a new type of therapy that uses the patient’s own immune system to fight cancer. This is despite the fact that ovarian cancer often has high numbers of T cells, an immune cell that has an ability to kill cancer cells. It is now known that T cells that are found in ovarian cancer are often stressed due to low amounts of oxygen, nutrients, and other critical factors. This stressed nature impairs the ability of the T cell to fight cancer. Therefore, identifying the ways through which T cells experience stressed conditions may lead to the development of new immune system-based therapeutic strategies for ovarian cancer. To this end, we have discovered a mutation in a molecule found in T cells that is associated with an improved outcome for ovarian cancer patients. Interestingly, this molecule appears to function within a poorly characterized stress-response system within T cells. Our study is therefore designed to understand the connection between this molecule and T cell activity in ovarian cancer, as we have found that T cells in which this molecule is removed have increased anti-tumor activity and delay disease progression. Thus, we expect that the completion of this work will drive the development new T cell-based therapeutic strategies in which stress response pathways have been altered in order to significantly improve the outcome of women with ovarian cancer.