Grant: Project Grant

BACKGROUND: The body can mount an anti-tumor immune response to eliminate cancer cells. However, cancer cells that are able to evade the immune system can continue to grow and progress to metastatic disease (gain the ability to spread form the primary site). Immunotherapy is a treatment strategy designed to block the ability of cancer cells to suppress the immune system. We have identified a protein, called GPNMB, that is able to promote the growth and spread of breast cancer cells. Our recent data suggests that it does so, in part, by suppressing anti-tumor immunity. OBJECTIVES: The goal of this grant is to understand how GPNMB that is expressed in breast cancer cells can impair the immune system and prevent tumor clearance. We will focus our efforts on: 1) defining the different immune cells that are present in cancer cells that do or do not express GPNMB, 2) identifying secreted proteins that are regulated by GPNMB and control the function of immune cells, 3) testing whether blocking GPNMB function can improve immunotherapy in breast cancer cells and 4) examining whether similar changes that we see in animal models of breast cancer also occur in human breast cancers. These approaches will uncover a number of mechanisms through which GPNMB helps breast cancer cells evade the immune system. SIGNIFICANCE: Immunotherapy is showing great promise in certain tumors, such as melanoma and lung cancer. This treatment strategy is now being tested in other types of cancer, including breast cancer. Understanding how tumors can suppress the ability of the immune system to eliminate cancer cells is critical to improving the efficacy of immunotherapy. In this way, understanding how GPNMB acts to suppress immune-mediated killing of cancer cells may reveal ways in which to better treat GPNMB-expressing breast tumors.