Research Interests:
The immune system is critically important for control of tumor growth. Cancer vaccines that generate tumor-specific immune responses are a new and promising method of cancer treatment. However, tumors develop ways to avoid recognition by the immune system and to hinder the effect of the vaccines. One of the most powerful of these is immunosuppression of the tumor host. The research of Dr. Gabrilovich and his colleagues is focused on understanding the mechanisms of tumor-associated immunosuppression and on development of new and effective cancer vaccines.
Dr. Gabrilovich and his co-workers are investigating abnormalities in the function of professional antigen-presenting cells, or dendritic cells (DC). These cells are responsible for induction of the antitumor immune response, but their differentiation and function are severely affected in cancer. Data generated in Dr. Gabrilovich's laboratory have demonstrated that defects in differentiation of DC are associated with accumulation of immature myeloid cells in tumor-bearing animals and patients with cancer. Under normal conditions, these cells represent an intermediate stage of myeloid cell differentiation. In cancer, however, they lose the ability to differentiate into mature myeloid cells, including granulocytes, DC, and macrophages. They become functionally defective and acquire the ability to suppress immune responses.
Dr. Gabrilovich's research is focused on two different aspects of immature myeloid cell biology in cancer. First, the researchers are trying to understand the signaling pathways that are responsible for accumulation and functional defects of immature myeloid cells in cancer. Second, they are investigating cellular and molecular mechanisms of T-cell suppression and tolerance induced as a result of abnormal differentiation of myeloid cells and abnormal DC function. Their recent findings have demonstrated that the Jak/STAT signaling pathway is critically important for normal myeloid cell differentiation in cancer. They also are studying the roles of other pathways important to DC differentiation and function, such as the Notch family of receptors and transcriptional regulators, transcription factor NF-kB, and small GTP-binding molecules such as Rac, Cdc42, and Rho. They have shown that reactive oxygen species produced by immature myeloid cells in vitro and in tumor-bearing animals in the presence of tumor-derived soluble factors are substantial contributors to the immunosuppression mediated by these cells in cancer. Another aspect of the research in Dr. Gabrilovich's laboratory is identification of new genes involved in normal differentiation of DC as well as defective differentiation and function of antigen-presenting cells in cancer.
Another large part of the research in Dr. Gabrilovich's laboratory is development of new tumor vaccines. The researchers are exploring several different approaches, including genetically modified DCs and combinations of apoptosis-inducing therapy and immunotherapy. The success of their in vitro and in vivo studies allowed translation of these approaches to the clinic. Several of their vaccines are now in clinical trials at Moffitt Cancer Center. These vaccines are used for certain patients with high-risk prostate cancer, small-cell lung cancer, or breast cancer. Dr. Gabrilovich and his research team are monitoring the immunological and clinical effects of these vaccines.
Clinical Interests:
Lung cancer, breast cancer, sarcoma, renal cell carcinima, melanoma, multiple myeloma