Dissection of an Inflammatory Immune Suppression Circuit Driven by Therapy-induced T Cell Activation
Immune checkpoint inhibitor (ICI) therapy and radiation therapy (RT) are treatments that stimulate the immune system to kill cancer cells. However, resistance to treatment remains a problem. We have discovered a new mechanism of resistance that is counterintuitively supported by T cells, which typically attack cancer cells. We found that T cells boost pro-tumor inflammation upon activation by ICI or RT. We aim to identify the factors that allow tumor-infiltrating T cells to increase pro-tumor inflammation. We will map the cellular and molecular "neighborhoods" in tumor tissue that are organized by T cells and contribute to tumor-promoting inflammation. We will determine the impact of this resistance pathway on the immunologic benefits of RT. This may update our understanding of how cancer immunotherapies work, thereby helping us to understand why treatments can fail. This work could also inspire new rational strategies that can convert tumor-promoting T cell activity to anti-tumor immunity.
