Li Tang

Metabolic reprogramming of exhausted T cells by IL-10 enhances anti-cancer immunity

Our immune system interacts with many diseases in a multidimensional manner involving substantial biological, chemical, and physical exchanges. Manipulating the disease-immunity interactions may afford novel immunotherapies to better treat diseases. My lab aims to develop novel strategies to engineer the multidimensional immunity-disease interactions (or termed ‘immunoengineering’) to create safe and effective therapies against cancer. We leverage the power of metabolic bioengineering, chemistry and material engineering, and mechanical engineering to achieve controllable modulation of immune responses. In this talk, I will first share our discovery of IL-10-Fc as a metabolic reprogramming agent that reinvigorates the terminally exhausted CD8⁺ tumor-infiltrating lymphocytes leading to eradication of established solid tumors and durable cures. This metabolic reprogramming strategy was also exploited to enhance CAR-T cell therapy to better treat solid tumors. I will next talk about our recent efforts in designing a metabolically armored CAR-T cell that secretes IL-10 to counter exhaustion-associated dysfunction in the tumor microenvironment for enhanced anticancer immunity. Our results establish a generalizable approach to counter T cell dysfunction through metabolic programming, which may overcome a major barrier in the current T cell-based immunotherapy in the clinic.