Primary AppointmentMicrobiology, Immunology, and Cancer Biology
Carter Immunology Center
Charlottesville, Virginia 22908
Identification of MHC-restricted tumor antigens / Control of T cell homing to tumors / Tertiary lymphoid structures and intratumoral immunity
Our research centers on understanding immune responses to tumors, and ways to enhance them for therapy. These responses depend on CD8 T lymphocytes, which recognize specific antigens on the tumor cell, leading to its destruction. Our work is in 3 major areas. First, we identify antigens that tumor cells display. These antigens are small peptides produced by degradation of intracellular proteins, which are then captured by MHC molecules and displayed at the surface. Recently, we showed that some of these peptides are phosphorylated, and displayed on cancer cells but not their normal counterparts. These peptides come from phosphoproteins associated with cellular signaling and growth control, and may be important targets for tumor immunotherapy. Some of these peptides are now in clinical trials at UVA as cancer vaccines. Second, we are evaluating the mechanisms that control the entry of CD8 T cells into tumors. A large fraction of tumors shows no detectable lymphocyte infiltration, and these patients have a worse prognosis. We identified the homing receptors that are upregulated on effector CD8 T cells activated in different secondary lymphoid organs, and established their importance in mediated entry of these cells into tumors. We also identified the homing receptor ligands expressed on tumor-associated vasculature and established that their expression is suboptimal. Current work is concerned with understanding the mechanisms that control their expression as a means to enhance T cell infiltration and tumor control. Finally, we have established that parts of tumor associated vasculature express molecules characteristic of lymph node vasculature. This leads to the infiltration and intratumoral activation of na?ve T cells, and can also lead to the formation of structures resembling lymph nodes inside the tumor. We are determining the importance of these structures in developing an ongoing intratumoral immune response that would augment control of tumor growth.