The tumor microenvironment (TME) is the primary arena in which tumor cells and the host immune system interact. Characterization of the nature of the immune responses in the human cancer microenvironment holds the key to understanding tumor immunity and designing and improving current cancer immunotherapy. Dr. Zou leads a multidisciplinary laboratory that investigates the human TME with the goal of understanding the 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 TME 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 Zou laboratory has studied human breast cancer, colon cancer, melanoma, ovarian cancer, and non-small cell lung cancer, and demonstrated genetic, epigenetic, metabolic, and autophagic mechanisms controlling APC and T cell trafficking and function in the tumor microenvironment - thereby impacting on tumor progression, metastasis, and therapeutic efficacy. Ongoing work is focused on identifying the molecular basis that defines different immune and biological phenotypes of tumors and shapes tumor responses to immunotherapy, chemotherapy, targeted therapy, and radiation therapy. These studies will eventually help identify previously unknown therapeutic targets and inform novel combinatorial therapeutic approaches that should expand the range of patients who respond to current immunotherapies.
Dr. Zou serves as Director of the Michigan Center of Excellence for Cancer Immunology and Immunotherapy, Co-Director of the Cancer Hematopoiesis and Immunology Program and directs the Immunologic Monitoring Core at the University of Michigan School of Medicine and Rogel Cancer Center. He also co-directs the Surgical Oncology Fellow Training (T32) program, through which clinical fellows are trained to become physician scientists, with a focus on cancer immunology and immunotherapy. At the national level, he was the AACR Cancer Immunology (CIMM) Chairperson 2019-2020 and served for 4 years as the Cancer Immunology Abstract Programming Chair for AAI. He has delivered more than 300 invited lectures at different institutions and conferences and published nearly 200 articles and book chapters – including 36 papers in Nature, Science, and Cell journal series. His laboratory is one of the most cited research teams in the field of immunology. His work has been highlighted by many scientific news agencies. He has developed an international reputation in human tumor immunology and immunotherapy as a successful and productive leader in these highly relevant fields.