Regulation of T cell antitumor immunity by tonicity signals from the tumor microenvironment

The tumor microenvironment is highly enriched in sodium chloride, but the effect of tonicity signals on anti-tumor immune cell responses remains unexplored. We have shown that hypertonicity modulates T cell signaling and induces a paralyzed anti-inflammatory T cell phenotype. Although this newly-discovered mechanism has dramatic implications for tumor control, the molecular sensors and effectors that couple hypertonicity to T cell paralysis are unclear. The project will investigate how a sodium chloride rich tumor microenvironment impairs productive TCR signals and T cell effector functions in humans with a particular focus on melanoma.