Rui Miao, PhD, Postdoctoral Fellow Boston Children's Hospital Cancer immunotherapy, which takes advantage of the patient’s own immune system to fight cancer, has achieved great success in the past decade. However, only a small portion of patients respond well to cancer immunotherapy. The success of cancer immunotherapy relies on killer lymphocytes, a subset of immune cells that recognize and directly kill tumor cells. Many tumor cells develop evading strategies to avoid attacks by killer lymphocytes. In addition, killer lymphocytes are functionally impaired in many cases. Therefore, further work is needed to understand how killer lymphocytes kill tumor cells and how tumor cells evade immune surveillance. Killer lymphocyte elimination of tumor cells relies on cell death-inducing enzymes, called granzymes. The goal of Dr. Miao’s proposed research is to investigate the underlying mechanisms by which granzyme M (GzmM), one of the most abundant and important granzymes in innate killer lymphocytes, triggers tumor cell inflammatory cell death called pyroptosis and augments anti-tumor immunity. She will assess how much GzmM contributes to tumor cell death and investigate whether and how tumor cells develop resistant mechanisms to GzmM. She will also explore the importance of GzmM in tumor control and the efficacy of cancer immunotherapies. Dr. Miao’s research will uncover novel mechanisms behind the interaction between tumors and the immune system and will provide the novel clinical potential to harness killer lymphocytes (GzmM)-mediated tumor inflammatory death in the tumor microenvironment to ignite an effective immune response to immunotherapy non-responding tumors and enhance the efficacy of current cancer immunotherapies. Projects and Grants Granzyme M activates Gasdermin E to trigger tumor cell pyroptosis and anti-tumor immunity Boston Children’s Hospital | All Cancers | 2022 | Judy Lieberman, M.D., Ph.D.