Haidong Dong, M.D., Ph.D.

Haidong Dong, M.D., Ph.D.'s research goal is to define regulatory mechanisms in tumor immunity.

Consequently, tumors enlarge and metastasize largely unchecked. The focus of our research is to understand how the immune system progressively loses its effectiveness in eliminating tumor cells.

Our efforts are directed towards developing strategies for blunting inhibitory regulatory pathways and enhancing anti-tumor immune responses. While our research is largely centered on tumors of the kidney, bladder, prostate and breast, the impact of my investigations extends to solid malignancies in general.

Research Project 1: Define the mechanisms by which immuno-regulatory molecules modulate in tumor immunity. Anti-tumor immune responses are dynamic and are subject to multiple levels of regulation, both positive and negative. Our interest is in developing strategies for compromising negative regulatory signals while boosting positive signals. Immuno-regulatory molecules of the B7 family play a central and critical role in immune responses. Our lab is intensively investigating the role of B7-H1 (CD274, PD-L1) in T cell responses to tumors. Studies from our lab have led to the development of the concept of B7-H1 blockade as an immunotherapy (Dong, et al, Nature Medicine 2002) which is currently in phase I clinical trial. In an effort to optimize and maximize efficacy of B7-H1 blockade as a tumor immunotherapy, our group is utilizing gene targeting (knockout and knockdown) and blockade (neutralizing antibody) approaches to identify optimal delivery modalities. We currently investigate how B7-H1 regulates priming, contraction and differentiation in T cell responses to primary and secondary metastatic tumors. Our research promises to open novel therapeutic options, including PD-1 and CD80 immune blockade, for the treatment of solid tumors.

Research Project 2: Identify predictive immune cell biomarkers to stratify cancer patients.

Certain FDA-approved tumor immunotherapies prolong the overall survival of a portion (about 15-20%) of melanoma or prostate cancer patients. However, to date it has not been possible to identify those patients most likely to respond to a particular therapy. There is an urgent and unmet need to identify biomarkers to effectively identify those patients most likely to benefit from certain immunotherapies.

In collaboration with clinical investigators from the Mayo Clinic Oncology team, we are identifying candidate immune cell biomarkers which may have predictive utility. Using systemic immunobiological approaches including microarray, nano-proteomics, multiplex and flow cytometry, we are assessing biomarkers for prognostic value.