The adaptive immune system serves to eliminate pathogens while sparing host tissue. The efficiency of this system is largely dependent on balance; unrestrained immunity can cause autoimmunity while a slow or absent response can lead to chronic infection and cancer. Regulatory T cells (Tregs) play a critical role in maintainin this balance through the suppression of self-reactive immune responses. Treg stability is crucial to maintain effective suppressive capacity. Neuropilin-1 (Nrp1), a surface receptor has emerged as an important mediator of Treg stability. Nrp1 binds the ligand, Semaphorin-4a (Sema-4a), leading to enhanced Treg stability intratumorally. In the absence of Nrp1:Sema4a ligation, Tregs lose stability and suppressive capabilities, leading to enhanced anti-tumor immunity and reduced tumor growth. The fate and function of Nrp1-deficient Tregs is unclear. This research proposal suggests experiments that will propel our understanding of how Nrp1 alters Treg stability, and will elucidate the molecular mechanisms leading to a distinct Treg cell population and reduced tumor growth. Understanding these mechanisms is of crucial importance in understanding tumor immunology, and in creating new targets for immunotherapy.
Regulatory T cells are essential for providing balance to the immune system. These cells provide protection against autoimmune diseases; however, they also prevent successful anti-cancer immunity. Our research seeks to understand how regulatory T cells are stabilized in the tumor microenvironment, and how the lack of stability affects the fat and function of regulatory T cells in cancer.
|Overacre-Delgoffe, Abigail E; Chikina, Maria; Dadey, Rebekah E et al. (2017) Interferon-? Drives Treg Fragility to Promote Anti-tumor Immunity. Cell 169:1130-1141.e11|
|Overacre, Abigail E; Vignali, Dario Aa (2016) T(reg) stability: to be or not to be. Curr Opin Immunol 39:39-43|