Grants - Designated Grants - California - 2015

Clare Yu, Ph.D. & Juliana “Julie” Wortman

Funded in Collaboration with Stand Up To Cancer (SU2C)

The goal of an exciting new form of immunotherapy is to get the immune system to kill cancer cells. When killer T cells arrive to kill tumor cells, some cancer cells are able to prevent this attack by inserting a protein that acts like a “key” (e.g., a PD1 ligand where ‘PD’ stands for Programmed Death) into a “keyhole” (e.g., a PD1 receptor) on the killer T cell.  Anti-PD1 immunotherapy drugs like nivolumab and pembrolizumab block the keyholes and prevent cancer cells from turning off the killer T cells. Such immunotherapy drugs are particularly effective when killer T cells have infiltrated the tumor. The goal of our project is to understand what features of the microenvironment of the tumor enhance the infiltration of killer T cells into the tumor. The tumor microenvironment, which includes cells, protein structures (like collagen fibers) made by some of these cells, blood vessels, and lymph vessels, typically provides a supporting environment for the tumor to grow. However, changes to the tumor microenvironment can inhibit the growth of the tumor and even lead to its demise. We will carefully characterize the spatial arrangements of the different types of cells and structures in the breast cancer tumor microenvironment in an effort to determine what enhances infiltration by killer T cells. Knowing this could lead to more effective immunotherapy.