Data from Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition

• DOI: 10.1158/2767-9764.c.7231101.v1
• Publication Date: 2024-05-13T14:31:04Z
• Authors: Forrest L. Baker; Kyle A. Smith; Preetesh L. Mylab...; Tiffany M. Zúñiga; Douglass M. Diak; Helena Batatinha; Grace M. Niemiro; Michael D. Seckeler; Charles R. Pedlar; Daniel P. O'Connor; Jamie Colombo; Emmanuel Katsanis; Richard J. Simpson
• Keywords: β2 adrenergic receptor

<div>Abstract<p>Exercise mobilizes cytotoxic lymphocytes to blood which may allow superior cell products be harvested and manufactured for cancer therapy. Gamma-Delta (γδ) T-cells have shown promise treating solid tumors, but there is a need increase their potency against hematologic malignancies. Here, we show that human γδ mobilized in response just 20 minutes of graded exercise surface phenotypes transcriptomic profiles associated with cytotoxicity, adhesion, migration, cytokine signaling. Following 14 days <i>ex vivo</i> expansion zoledronic acid IL2, had enhanced effector functions demonstrated activity multiple tumors <i>in vitro</i> leukemia-bearing xenogeneic mice. Infusing humans the β1+β2-agonist isoproterenol administering β1 or β1+β2 antagonists prior revealed these effects β2-adrenergic receptor (AR) dependent. Antibody blocking DNAM-1 on expanded T-cells, as well ligands PVR Nectin-2 leukemic targets, abolished antileukemic exercise. These findings provide mechanistic link between exercise, β2-AR activation, manufacture T-cell adoptive therapy malignancies.</p>Significance:<p>Exercise via signaling allows generation potent product highly malignancies.</p></div>