Joe N. Frost, PhD, Postdoctoral Fellow Memorial Sloan Kettering Cancer Center Immune cells communicate through the production of soluble mediators such as cytokines. Traditionally, cytokines are divided into those that enhance systemic and local inflammation and immunity (pro-inflammatory), or dampen inflammation to prevent tissue damage and support tissue repair (anti-inflammatory). Therapeutic targeting of cytokine signalling pathways has been pursued as a means to treat a diverse range of diseases including cancer, autoimmunity, inflammatory and infectious diseases. A limitation for extending cytokine-based therapies to a wider range of diseases is the complexity and pleiotropy of cytokine functionality, as it becomes increasingly apparent that a given cytokine can exert both pro- and anti-inflammatory effects. Dr. Frost’s proposal will test a hypothesis that the ‘cellular source of the cytokine matters’. To gain better understanding of how the cellular source of cytokines modulates their function in vivo, he aims to explore a role for the classically pro-inflammatory cytokine, IFN-gamma, and anti-inflammatory cytokine, IL-10 – when produced by regulatory T cells, a specialized anti-inflammatory cell type, in regulation of neuroinflammation. Specifically, he will explore roles for Treg-produced IFN-gamma and IL-10 in controlling neuroinflammation and examine their effects on microglia, an essential accessory cell type supporting neuronal functions. Given the important role of inflammation in promoting and opposing cancer progression and the reported production of IFN-gamma by intratumoral Treg cells in response to immunotherapy, the results of this study will elucidate a role of Treg cells and their secreted products in glioma and other cancer types. Projects and Grants Cellular source dependent function of interferon-gamma in neuroinflammation Memorial Sloan Kettering Cancer Center | All Cancers | 2022 | Alexander Rudensky, Ph.D.
