FIGURE 4 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: 10.1158/2767-9764.25810089.v1
• Publication Date: 2024-05-13T14:22:10Z
• 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

<p>ISO infusion enhances the antileukemic activity of <i>ex vivo expanded</i> Vγ9Vδ2+ T-cells <i>in vitro</i> and vivo</i>. <b>A,</b> Schematic experimental design for vivo</i> experiments. <b>B,</b> The total number (1 × 10<sup>6</sup>) cells isolated before (REST) during final 5 minutes ISO at day 0, generated in expanded cell products after stimulation with ZOL+IL2 14 days. relative to γδ PBMC fractions 0. cellular composition T-cell 14. proportions naïve (N), CM, EM, CD45RA+ EMRA among days expansion (<i>n</i> = 7). <b>C,</b> anti-tumor against K562, Daudi, U266 via flow cytometry–based assays. Significance indicated by ** (<i>P</i> < 0.01) *** 0.001). <b>D,</b> To determine GvL effect Vγ9Vδ2+, NSG-IL15 mice were injected REST or (10 challenged 1 10<sup>6</sup> luciferase tagged human chronic myeloid leukemia (K562-luc). A subset each group also provided weekly injections ZOL (REST+ZOL; ISO+ZOL; VEHICLE +ZOL). BLI (photons/second) scores, TFS, change BW, probability survival injection without sensitization 7–8/group<b>).</b> significant difference from EX+ZOL EX conditions * <sup>#</sup>, respectively (all significantly different vehicle controls). OS controls (TFS; EX, EX+ZOL, REST+ZOL significance a single marker). <b>E,</b> Representative bioluminescence images leukemia-bearing that received (from left right) vehicle, + ZOL, T-cells, ZOL. intensity on scale low (purple) high (red). Data are represented as mean ± SEM; *, <i>P</i> 0.05; **, 0.01; ***, 0.001; ****, 0.0001 Students two-tailed paired <i>t</i> test (B); Repeated measures two-way ANOVA LMM Bonferroni <i>post hoc</i> (C–D); log-rank (Mantel–Cox) (D).</p>