The research of Haidong Dong, M.D., Ph.D., is focused on defining regulatory mechanisms that influence antitumor immunity. The long-term goal of his laboratory is to understand the molecular and cellular regulatory mechanisms in tumor-immune cell interactions and translate basic research observations into effective cancer immunotherapies.
Two main factors contribute to the failure of tumor immunity: First, the immune system is rendered ineffective by the overwhelming presence of tumor cells; second, tumor cells develop resistance to immune responses. The focus of Dr. Dong's research is on understanding how the immune system progressively loses its effectiveness in eliminating tumor cells and how tumor cells acquire resistance to multiple treatments.
To achieve its research goals, Dr. Dong's group is intensively utilizing gene targeting (knockout and knockdown) strategies, monoclonal antibody blockade/ligation, protein interaction/identification assays, microarray, nanoproteomics, multiplex cytokine assays and flow cytometry.
Dr. Dong's research is funded by the National Institutes of Health and Mayo Clinic.
- How do we generate and maintain a durable antitumor immunity? Cytotoxic T lymphocytes (CTLs) are the major defense immune cells involved in the elimination of tumor cells. A CTL response to tumor cells is a dynamic process initiated at the emergence of tumor cells and regulated until the late stage of tumor metastasis. Tumor cells and surrounding stromal cells provide critical signals that influence the generation, differentiation and duration of CTL responses to tumors. Research by Dr. Dong and his team is focused on defining the nature and function of these signals and developing new approaches to improve the anti-tumor activity of CTLs.
- How do we overcome tumor resistance to cytotoxic therapy (immunotherapy, chemotherapy and radiotherapy)? Many human tumor cells originate from and develop in chronic inflammatory environments. Some proinflammatory factors show immune-inhibitory function by increasing the expression of immune-regulatory molecules in tumor cells. The immune-regulatory molecules in turn render tumor cells resistant to cytotoxic drugs or reagents. Dr. Dong's group is working to define how immune-regulatory molecules regulate the survival of tumor cells and identify new therapeutic targets in tumor cells that would reverse the drug resistance of tumor cells.
Significance to patient care
Efforts by Dr. Dong and his team are directed toward developing strategies for improving tumor immunotherapy and blunting tumor resistance to cytotoxic therapies, such as immunotherapy, chemotherapy and radiotherapy. While their research is largely centered on tumors of the kidney, bladder, prostate and breast, as well as on melanoma, the impact of their investigations extends to leukemia and solid malignancies in general.