Research Associate Professor, Lurie Cancer Center; Feinberg School of Medicine
TRIST-Gastrointestinal Cancers,Cancer Prevention
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Cancer Immune Surveillance, Immune Tolerance, and Inflammation
The limited success of cancer vaccines can be explained by the pathogenic nature of immunity in cancer, dominated by tumor promoting inflammatory reactions and immune tolerance. Our major interest is the immune pathology of colon cancer, but we are also engaged in studies in pancreatic, lung, and breast cancer. Our research is both translational and basic, using surgical and blood specimens from human cancer patients as well as mouse models of cancer. The combined use of human samples and mouse models permits us to test hypotheses based on human observations in mice, and go back and validate the relevance of our observations in human cancer patients. Our long term goal is to understand the immune pathologies of distinct human cancers and use this information for therapeutic intervention.
A major focus of our research is the regulation of inflammatory responses in cancer. Here the cross talk between T-regulatory cells, mast cells and dendritic cells define the level and quality of inflammation and immune suppression. We have identified both pathogenic and protective Treg subsets with pro-inflammatory and anti-inflammatory properties. The two subsets are distinguished by their expression of specific transcriptional factors and cytokines. The focus of our study is Treg subsets, signaling in Treg, and the contribution of antigen presenting cells and cytokines to Treg functions and inflammation.
We are interested in the role of cancer inflammation and in particular of mast cells in cancer. Mast cells are tissue sentinel cells and central effectors of inflammation and tissue remodeling. We are investigating the contribution of mast cells to the initiation and progression of cancer in the colon, intestine, and pancreas. We have used mast cell specific mutations to enhance or down modulate tumor promoting properties of mast cells. In this respect we are characterizing the role of cKIT signalling, and Wnt pathway in mast cell funciton. We have evidence that mast cell specific mutations contribute to progression of colorectal cancer in transgenic mouse models. Mechanisms of cancer progression are under investigation. We have collaborations with other laboratories to determine the role of microbiota in regulation of inflammation and impact on colon cancer.
We are actively engaged in immune monitoring of cancer patients undergoing immune modulating therapies. This is a close collaboration with oncologists at Northwestern University and involves clinical trials with checkpoint blockade agents, antibodies that inhibit CTLA4 and PD1. In this effort we benefit from a close collaboration with the German Cancer Research Center (DKFZ) in Heidelberg, and make use of characterized peptides that are recognized by pre-existing tumor specific memory T-cells to follow specific anti-tumor immunity. The use of these peptides for developing future vaccines is a major goal of this ongoing collaboration. We are anticipating similar efforts in breast and prostate cancer.