The research of Haidong Dong, M.D., Ph.D., is focused on cancer immunology and immunotherapy. The long-term goal of his laboratory is to understand the regulatory mechanisms shaping anti-tumor immunity and translate discoveries in cancer immunology into effective cancer immunotherapy.

Dr. Dong's early work addressed the Hellstrom paradox — an enigma in cancer immunology — the coexistence of immune cells and growing tumors. He co-discovered B7-H1 (also called PD-L1) in 1998 and was the first to define a role of B7-H1 in cancer immune evasion. And he coined the concept of B7-H1 blockade therapy of cancer in 2002. This discovery provided an explanation for the Hellstrom paradox: Despite being surrounded by immune cells in tissues, cancer cells can escape the immune attack by using B7-H1 in tumor microenvironments to dampen the function of immune cells.

Currently, the research areas of Dr. Dong's lab are on defining:

• The biochemical responses to immune checkpoint inhibitors in human immune cells
• The synergistic effects of combination therapy (chemotherapy or radiation therapy with immunotherapy)
• The molecular mechanisms in immune cell-mediated cytotoxicity against cancer cells
• The tumor-intrinsic functions of PD-L1 in tumor biology and resistance to therapy

Dr. Dong's translational research is expected to deliver new biomarkers to predict and monitor patient responses to cancer immunotherapy, new therapeutic targets to overcome cancer resistance to immunotherapy, and new rational combined cancer therapy. His research is funded by the National Institutes of Health and Mayo Clinic.

Focus areas

• Defining the mechanisms of immune responses to therapies in patients with advanced cancer. Naturally occurring (endogenous) tumor-reactive immune responses are present and protective, but generally invisible. In most cases with progressive cancers, endogenous tumor-reactive immune cells remain quiescent. Dr. Dong's research group is addressing the therapeutic impacts (immunotherapy, surgery, radiation and chemotherapy) on the patient's own immune system, and seeking a better way to promote and maintain an effective anti-tumor immunity in patients.
• Identifying the mechanisms responsible for cancer resistance to cytotoxic therapy. Development of resistance to therapy is a hallmark feature of human cancer. Since most cancer treatment induces cell death in cancer cells (cytotoxic therapy), cancer cells gradually and adaptively gain mechanism to survive under cytotoxic therapy. Traditionally, the emergence of chemoresistance and immunesuppression are considered as parallel and unrelated events. However, recent studies indicate that certain immune checkpoint molecules also regulate the sensitivity of cancer cells to chemotherapy or radiation therapy. Dr. Dong's research group is working to determine how cancer cells gain therapy resistance or sensitivity through immune regulatory molecules intrinsically, and to develop rational combination therapy to overcome cancer resistance.

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.