Professor, Eppley Institute
Courtesy Appointment - Department of Biochemistry & Molecular Biology
PhD Southern Illinois University, 1992
A significant advance in the area of cancer immunology has been the characterization of tumor-associated antigens recognized by T lymphocytes. These tumor-associated antigens have been found to be peptides, derived from tumor-specific proteins, that are bound to cell surface receptors called major histocompatibility complex (MHC) molecules. Once a T lymphocyte has recognized an MHC molecule that bears a tumor peptide, it lyses the cell to prevent further spread of the malignancy. To transport a tumor peptide to the cell surface, the class I MHC heavy chain must first bind to it inside the cell, assisted by a group of proteins. Our laboratory is studying the assembly of the class I MHC molecule with peptides and the intracellular trafficking of the class I MHC molecule, with the goal of identifying ways in which those processes influences the type and quantity of tumor-specific antigens that are presented to T lymphocytes, and with the goal of increasing the expression of MHC molecules on tumors. Our laboratory has discovered that amyloid precursor-like protein 2 influences MHC class I surface expression and simultaneously affects the growth of certain kinds of cancer cells, and therefore it is a therapeutic target from both immunology and cancer biology perspectives.
We are also using the knowledge gained from our studies on T cell-mediated immunity in our development of better immunotherapies (including cytokine and chemokine immunotherapies) for cancer, as well as for infectious diseases such as influenza. For pancreatic cancer and breast cancer, new approaches to cancer therapy that can be used in conjunction with existing treatment strategies are urgently needed. As an adjunct therapeutic approach, immunotherapies can potentially be used to attack tumors regionally or systemically, with minimal side effects. Dendritic cells are the major cells responsible for initiating an effective response against tumors, via presentation of antigens from engulfed tumor cells to T lymphocytes. The localization and numbers of dendritic cells are determined by chemokines and cytokines. Dendritic cells, as well as T lymphocytes, are attracted by the chemokine CCL21, and the cytokine Fms-like tyrosine kinase-3 ligand (Flt3L) causes in vivo expansion of DCs. We are working to determine the effects of CCL21 and Flt3L on dendritic cell and T lymphocyte activity against pancreatic and breast cancers.