Regulation of T cell antitumor immunity by tonicity signals from the tumor microenvironment (P18)

肿瘤微环境高度富集氯化钠，但强直信号对抗肿瘤免疫细胞反应的影响尚不清楚。我们已经证明高渗调节T细胞信号传导并诱导瘫痪抗炎T细胞表型。尽管这一新发现的机制对肿瘤控制具有重大意义，但将高张力性与T细胞麻痹相结合的分子传感器和效应物尚不清楚。该项目将研究富含氯化钠的肿瘤微环境如何损害人类的TCR信号和T细胞效应物功能，特别关注黑色素瘤。

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.