The immune system is critical in the fight against cancer. The T cells of the immune system are capable of recognizing cells that have become malignant and killing them. In this way, the immune system prevents cancers from occurring. However, the tumor can protect itself from being cleared by the immune system by sending inhibitory signals to the T cells. One of the most notable inhibitory signals used by tumors is PD-L1. PD-L1 is a gene that is upregulated on many types of cancer cells, including ovarian cancer cells. PD-L1 interacts with another molecule, PD-1, which is expressed by T cells. When the PD-1 expressing T cells meet a PD-L1 expressing cancer cell, the T cells become suppressed and do not kill the cancer cells. Drugs that block PD-1 or PD-L1, such as Keytruda (pembrolizumab) and Tecentriq (atezolizumab), are helping to lead a revolution in cancer treatment. These drugs have achieved complete and durable tumor regression for a number of patients with a wide variety of cancers, including non-small cell lung cancer, melanoma, renal cell cancer. They are now being employed in ovarian cancer with some success already reported when used alone or in combination with other cancer fighting drugs.
Despite the overwhelming importance of PD-L1 as a way for cancers to evade the immune system, little is known about what controls PD-L1 on cancer cells. This is important to understand because it could tell us how this pathway becomes utilized by cancers, and could even lead to new and better ways to control the pathway and prevent tumors from using it to evade immune clearance. The goal of this project is to determine how ovarian cancer cells turn on PD-L1. The significance of these studies is that they will be one of the first to identify a pathway that controls PD-L1 expression, and will lead to a better understanding of how PD-L1 is regulated on ovarian cancer cells. This will provide much needed insight into one of the mechanisms used by cancer to evade immunity. This mechanism may also provide a new target for modulating the expression of PD-L1, and could be used for improving cancer immunotherapy by enabling a way to downregulate PD-L1 on cancer cells.