Programmed cell death and immunity in cancer: The ability of the immune system to recognize tumor cells as malignant entities is the foundation for the development of novel immunotherapies that have revolutionized cancer medicine. Certain types of cytotoxic anticancer therapies activate inflammatory cell death that facilitates immune-mediated recognition of tumors. The cytokines and danger molecules released during immunogenic cell death are vital for successful tumor-antigen presentation and adaptive immunity. In response to cytotoxic therapies tumors undergo programmed cell death that includes apoptosis, autophagy, pyroptosis and necroptosis. Most cytotoxic anticancer therapies have poor specificity for tumor cells and activate multiple types of programmed cell death. Moreover, different tumor types respond differently to cytotoxic therapies. As a result, it is difficult to identify relevant types of cell death that generate long-lasting antitumor immunity. The first goal of my lab’s research is to understand the host factors, immunological processes and tumor-intrinsic genetic factors that dictate immunotherapeutic outcome subsequent to activation of cell death.
Programmed cell death and immunity in virus infection: Viruses are ubiquitous genetic parasites in the biosphere, and virtually all organisms have evolved multiple defense mechanisms to cope with these parasites. At the heart of antiviral defenses are host-encoded receptors that can sense pathogen-associated molecular patterns to activate antiviral signaling cascade and programmed cell death, whereby an infected cell “commits altruistic suicide” to prevent spread of the virus to neighboring cells. Moreover, infected and dying cells can also secrete immuno-modulatory molecules that alarm the immune system. It is not known how different types of programmed cell death dictates antiviral immunity. The second goal of my lab’s research is to dissect mechanisms by which programmed cell death shapes adaptive antiviral immunity.
