PDL-1 Expression on Tumor Cells Mediates C8 Cytotoxic T Cell (CTL) Resistance
Malignant Peripheral Nerve Sheath tumors (MPNSTs) are aggressive soft tissue sarcomas resistant to most cancer treatments. Tumors can mask themselves from the immune response by expressing specialized proteins that inhibit the immune response. PDL-1 is one such protein and interacts with a receptor on T cells, PD-1, which inhibits T cell activation and allows host cells to evade immune-surveillance. This is a common method for tumors (e.g. malignant gliomas) to evade the immune response. Our preliminary data indicated that some MPNST tumor lines express high levels of PDL-1, which may suppress the immune response.
The focus of this project is to evaluate PDL-1 expression levels on multiple human and murine MPNST tumor lines by multicolor flow cytometry. We will also evaluate how oncolytic Herpes simplex virus (oHSV) infection influences this PDL-1 expression. Viruses often pull receptors off the surface of infected cells to hide from the immune response. In the case of PDL-1, the virus may upregulate this marker. The final phase of Taylor’s project will involve evaluating how PDL-1 expression on the tumor cells impacts the CD8 T cell’s functional response to the tumor cells. For these studies, she will mix T cells with tumors that have different levels of PDL-1 expression in cell culture assays. We will measure T cell activity by measuring surface markers of T cell activation by flow cytometry and chemicals (interferon and cytokines) produced by the activated T cells. These results will be used as a foundation for pre-clinical models to evaluate the effectiveness of combination oHSV and anti-PDL therapy.