Elucidating the Role of Neuropilin-1 in Intratumoral Regualtory T Cell Stability

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

? DESCRIPTION (provided by applicant): 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.