Metabolic Factors

Cancer cells differ from normal cells in the metabolic machinery used to support cell proliferation and survival. Although glycolysis is a physiologic response to hypoxia in health cells, cancer cells constitutively take up glucose and produce lactate regardless of oxygen availability. Several studies report that metabolic interplay between tumor and immune cells in the tumor microenvironment plays an important role in immune response regulation. Metabolic programming of lymphocytes increases energy demand and is crucial for triggering of effector T cell activation.  In addition, accumulation of toxic metabolites in the TME can also impact tumor and immune cell interactions. Acidosis in the TME can suppress proliferation and cytokine production in cytotoxic T cells (CTL) and limit their activity. High serum lactate dehydrogenase (LDH) concentrations correlate with poor outcomes to immunotherapies. Lactic acid and low local Ph can impair crucial T cell functions such as cytokine production (I-2, IFN-γ), proliferation and lytic activity.

Studies include:

  • Screen for tumor metabolites that affect lymphocyte  in response to drug candidate treatment

  • Discover chemokines and immune checkpoint interactions

  • Combination studies of chemokines and immune checkpoint blockade

  • Engineered chemokine receptors and chemokines in our HLA-matched CTL and tumor lines