Uncovering New Ways to Harness the Power of the Body’s Immune System to Fight Cancer
Besides their well-characterized role as initiators of adaptive immune responses, dendritic cells (DCs) also play a critical role in the induction and maintenance of tolerance to self and tumor antigens. A failure of the first role will produce immunodeficiency permitting unwanted tumor growth, while tumors are known to exploit DC-mediated tolerance to evade the immune system. As such, DCs have been increasingly tested for the development of cancer vaccines. However, current DC-based vaccines remained largely unsuccessful mainly due to lack of generation of effector and more importantly memory CD8 T cells to control tumor growth. Understanding the underlying mechanisms for how DCs-mediated T cell responses is regulated is critical to improve the efficacy of DC-based vaccine.
Recent studies have suggested catenin signaling as a potential mechanism for controlling DC-mediated T cell responses. Dr. Aimin Jiang is leading new research that hypothesizes that the β-catenin signaling pathway in DCs similarly regulates anti-tumor T cell immunity. To test this hypothesis, Dr. Jiang’s team has generated a series of CD11c(DC)-specific knockout mice that either activate or inactivate the β-catenin pathway. Indeed, mice with β-catenin mutations in DCs showed increased tumor growth and diminished CD4 and CD8 T cell response, suggesting that β-catenin negatively regulates DC-mediated T cell responses. More importantly, β catenin-active mice failed to generate strong memory CD8 T cell responses, suggesting that β-catenin negatively regulates CD8 memory responses. As DC-based vaccines have now being approved for cancer treatment, this project will have an immediate impact on helping design new ways to improve upon current DC vaccines.