Matteo Gentili, PhD, CRI-Bristol Myers Squibb Fellow The Broad Institute Area of Research: All Cancers A central question in cancer biology is how the immune system is naturally alerted to the presence of tumors. Mounting evidence suggests that the recognition of tumor DNA—a potent activator of the innate immune system, our body’s first line of defense—in the tumor microenvironment plays a fundamental role in this process. Due to their high replication rate, cancer cells often accumulate this misplaced DNA that activates a protein called STING. While STING activation in tumors is fundamental to drive immune-mediated tumor elimination and successful immunotherapy responses, recent evidence suggests that STING activation can also contribute to tumor metastasis. Given this paradox, Dr. Gentili aims to improve our understanding of STING’s basic biology in order to aid the development of immunotherapies to take advantage of the pathway’s potential. Specifically, he is pursuing a systems biology approach—incorporating genetic screens, protein studies, and tumor models—to define the molecular players that regulate STING activation. Overall, his team hopes that their findings will deepen our understanding of this fundamental immune pathway and pave the way for the rational design of more effective STING-targeting strategies for patients with cancer. Projects and Grants A systematic study of STING pathway components and their role in cancer immunotherapy Broad Institute of MIT and Harvard | All Cancers | 2020 | Nir Hacohen, PhD
