The Weiping Zou Research Laboratory
The tumor microenvironment is the primary arena in which tumor cells and the host immune system interact. Characterization of the nature of immune responses in the human cancer microenvironment holds the key to understanding tumor immunity and designing and improving current cancer immunotherapy. Weiping Zou leads a multidisciplinary laboratory that investigates the human cancer microenvironment with the goal of understanding genetic, epigenetic, and metabolic nature of human tumor immune responses and developing mechanism-informed combination therapies for cancer. The laboratory has demonstrated that the interaction between tumor cells and the host immune system fosters tumor immunosuppressive networks and results in cancer progression and therapeutic resistance. Their studies of cancer infiltrating T cell subsets including regulatory T cells (Tregs), Th17, Th22, and CD8+ effector T cells, and antigen presenting cells (APCs) including dendritic cells (DCs), macrophages, myeloid derived suppressor cells (MDSCs), and molecular signatures have elucidated major cancer immunosuppressive networks and therapeutic resistance mechanisms and allowed for determination of clinically targeting these mechanisms to effectively treat cancer patients. Their work including the first demonstration of the expression, regulation, and functional blockade of PD-L1 (B7-H1) in the human cancer microenvironment and human tumor draining lymph nodes and their early concept of combinatorial immunotherapeutic strategy has laid the scientific foundation for current cancer immunotherapy and has provided rationales for novel combinations.
In recent years, the laboratory has identified and characterized “hot” and “cold” subsets of human ovarian and colon cancers based on the levels of T cell tumor infiltration, and defined epigenetic and metabolic mechanisms controlling effector T cell tumor trafficking and function. Ongoing work is focused on identifying the molecular basis explaining different tumor phenotypes, immunotherapeutic response, chemotherapy resistance, and radiation resistance with an eye towards new combinatorial therapeutic approaches that should expand the range of patients who respond to current immunotherapies including PD-L1 and PD-1 blockade.