New compound boosts immunotherapy efficacy in immune-suppressive triple-negative breast cancer

Immunotherapies involving the programmed death receptor 1 (PD-1) protein have shown promise in helping some patients with triple-negative breast cancer. The PD-1 protein, found on the type of immune cells called T cells, helps keep the body’s immune responses in check, which limits their ability to attack cancer cells. As a result, immune-based approaches to cancer treatment are limited by the inherently immunosuppressive nature of the tumor microenvironment, which can cause patients to develop resistance to the treatments and render them ineffective. A team led by Winship Cancer Institute researcher Yong Wan, PhD, the Emory School of Medicine Endowed Professor in the Department of Pharmacology and Chemical Biology, recently reported a significant development in the search for ways to help the immune system fight cancer. Wan’s team used multi-omics analyses to find that the unusually high expression of the enzyme CD73 in triple-negative breast cancer correlates with post-translational modifications of proteins and that the upstream protein OTUD4 is a novel target for improving the anti-cancer immune response. To target the interaction between OTUD4 and CD73, they developed a new type of small molecule drug, ST80, and demonstrated its potential to reinvigorate the activity of CD8+ T cells, the immune cell which targets viruses and enhance tumor sensitivity to PD-L1 treatment. The study sheds light on important biological processes and presents a novel strategy to overcoming immune-suppressive triple-negative breast cancer.