Research of Gabrilovich laboratory is focused on understanding the mechanisms of tumor-associated immunosuppression as well as on the development of new effective cancer immunotherapeutics.
Specifically, they are working on several different but closely linked projects:
- Investigation of differentiation of professional antigen presenting cells - dendritic cells (DC). These cells are responsible for induction of antitumor immune response. However, their differentiation and function in cancer is severely affected. They are studying signal transduction mechanisms involved in DC differentiation: the role of transcriptional regulator Notch, transcription factors NF-kB, and JAK-STAT pathway;
- Understanding the biology and mechanism of action of myeloid-derived suppressor cells (MDSC) that accumulate in cancer patients and tumor-bearing mice. These cells are shown to be one of the major factors in the development of tumor non-responsiveness. Gabrilovich laboratory is studying the mechanisms of their expansion and differentiation, specifically focusing on the role of retinoblastoma (Rb) gene in this process. They also investigate the mechanisms of T-cell tolerance induced by MDSC and potential therapeutic approaches to eliminate MDSC in pre-clinical and clinical settings;
- Investigation of the effect of tumor microenvironment on differentiation and function of myeloid cells including immature myeloid cells, tumor associated macrophages and dendritic cells. They are studying the role of different factors (tumor endothelium, cytokines, hypoxia) that could be responsible for abnormal differentiation and function of these cells in tumor milieu.
- Study of the role of lipid accumulation in the abnormal function of myeloid cell in cancer;
- Investigation of the role of reactive oxygen species (ROS) in tumor associated immune defects. They are trying to identify the molecular mechanisms of increased ROS production in myeloid cells in cancer and it potential effect on effector cells;
- Development of new methods of cancer immune therapy. Specifically, they are focused on combination of cancer vaccine or adoptive T-cell therapy with conventional chemotherapy and radiation therapy;
- The Gabrilovich lab is involved in several clinical trials of DC based vaccines