Presenters: Idris Alabi ; Richard Warner ; Daniel Blackmore
Authors: Richard Warner, Idris Alabi, Daniel Blackmore, Tyler Trent
Faculty Advisor: Richa Warn
Institution: Dixie State University
Recently, advancements in cancer treatments have focused on combination therapies including targeted therapy. In melanoma, immunotherapy has been used to recover immune signaling lost due to CTLA-4 and PD-1. These are examples of targeted immunotherapy. B7-H3 is another immune protein that is overexpressed and may be targetable in melanoma. Our goal is to follow up on the finding that midkine, a soluble growth factor, demonstrates interactions with B7-H3. However, the functional effects of this interaction have not been identified. Exploring this link could be beneficial to the development of new immunotherapies. Midkine plays a role in growth, survival, migration, and differentiation in cells. It is overexpressed in tumors and has been suggested to contribute to malignant characteristics. B7-H3 inhibits the activation of T-cells and autoimmunity. We have observed high levels of B7-H3 expression across many melanoma cell lines. B7-H3 has also been identified as a marker of poor prognosis and associated with shorter survival time and increased recurrence in other cancers. We will be using T-cell growth assays to explore the effect of midkine signaling on B7-H3. Meanwhile, we will also determine how midkine affects the immune-related functions of B7-H3. These assays will be performed on four different cell lines composed of A375, CACL, C8161, and SK-MEL2. These cell lines vary in their expression of B7-H3 and midkine. Specifically, we will examine how high or low levels of these proteins contribute to cell survival and growth of melanoma cells in which we have observed over-expression. Identifying a specific B7-H3-interacting protein with a targetable relationship, which we predict for midkine, would have novel implications for tumor-immune signaling and could provide insights for expanded immunotherapy treatments as well.