My laboratory is focused on understanding the molecular mechanisms and cellular interactions that promote immunosuppression to inhibit immune responses. Our goal is then to use this information to design therapies that block these suppressive pathways to broadly restore immunity to eliminate cancer and chronic viral infections. It is becoming increasingly evident that host-based immunosuppressive factors induced during cancer and chronic virus infections inhibit T cells from curing the disease. Importantly many of the same factors suppress the immune responses against multiple chronic diseases (including chronic viruses and cancer), suggesting that the underlying mechanisms of immune dysfunction are conserved and that it will be possible to simultaneously develop immunotherapies that target central drivers of immunosuppression to fight both chronic viruses and tumors.
In addition to immunosuppression, cancer and chronic infections are associated with inflammation that is increasingly being recognized to further exacerbate immune exhaustion and promote disease progression. Although these two seemingly opposing programs of inflammation and immunosuppression co-exist and each associated with worsened disease, their relationship is unclear. Our group discovered that in addition to their critical antiviral and immunostimulatory roles, type I interferons (IFN-I) are core regulators of the diverse suppressive pathways that suppress immunity during viral persistence and demonstrated that IFN-I signaling could be blocked to restore immune health and control chronic virus infection. We are currently extending these studies to cancer and cancer immunotherapy to understand how chronic IFN alters anti-tumor immunity and the potential use of distinct IFN signatures as biomarkers of therapeutic efficacy.