GSE263181 Exercise-induced beta2 adrenergic receptor activation enhances the anti-leukemic activity of expanded gamma-delta T-Cells via DNAM-1 upregulation and PVR-Nectin-2 recognition

Contributors : Forrest L Baker ; Kyle A Smith ; Preetesh L Mylabathula ; Tiffany M Zuniga ; Douglass M Diak ; Helena Batatinha ; Grace M Niemiro ; Michael D Seckeler ; Charles R Pedlar ; Danie P O'Connor ; Jamie Colombo ; Emmanual Katsanis ; Richard J SimpsonSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensExercise mobilizes cytotoxic lymphocytes to blood which may allow superior cell products to be manufactured for cancer therapy. Gamma-delta T-cells have shown promise for treating solid tumors, but there is a need to increase their potency against hematologic malignancies. Here, we show that human gamma-delta T-cells mobilized to blood in response to just 20-minutes of graded exercise have surface phenotypes and transcriptomic profiles associated with cytotoxicity, adhesion, migration and cytokine signaling. Following 14-days ex vivo expansion with zoledronic acid and interleukin (IL)-2, exercise mobilized gamma-delta T-cells had surface phenotypes and transcriptomic profiles associated with enhanced effector functions, and demonstrated superior cytotoxic activity against multiple hematologic tumors in vitro, and in vivo in leukemia bearing xenogeneic mice. Infusing humans with the beta1+beta2-agonist isoproterenol and administering beta1 or beta1+beta2 antagonists prior to exercise revealed these effects to be beta2-adrenergic receptor (AR) dependent. Antibody blocking of DNAM-1 on expanded gamma-delta T-cells, as well as the DNAM-1...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research