Figure 3 from IFNγ Production by Functionally Reprogrammed Tregs Promotes Antitumor Efficacy of OX40/CD137 Bispecific Agonist Therapy
Imianowski CJ., Kuo P., Whiteside SK., von Linde T., Wesolowski AJ., Conti AG., Evans AC., Baird T., Morris BI., Fletcher NE., Yang J., Poon E., Lakins MA., Yamamoto M., Brewis N., Morrow M., Roychoudhuri R.
<p>OX40/CD137 dual agonism results in decreased CD25 expression and IL2 responsiveness of Tregs. <b>A,</b> Representative histograms and replicate measurements showing CD25 expression on CD4<sup>+</sup> Tregs from the spleen (left) and tumor-draining lymph node (right). <b>B,</b> Schema showing setup of <i>ex vivo</i> IL2 assay (left), replicate measurements of Foxp3-GFP expression (center), and Treg count (right) after 4 days in culture with the indicated concentrations of IL2. <b>C,</b> Schema representing treatment schedule of tamoxifen, FS120m, and rIL2/anti-IL2 mAb complex. <b>D,</b> Representative plots (left) and replicate measurements (right) of the percentage of RFP<sup>+</sup> SP exTregs (GFP<sup>−</sup>) out of total RFP<sup>+</sup> cells in the tumors and spleens of reporter mice treated according to <b>C</b>. Data were analyzed by unpaired Student <i>t</i> test (<b>A</b>), unpaired Student <i>t</i> test with Bonferroni–Dunn correction for multiple comparisons (<b>B</b>), and one-way ANOVA with Tukey correction for multiple comparisons (<b>D</b>). Bars and error are mean and SEM. *, <i>P</i> ≤ 0.05; **, <i>P</i> ≤ 0.01; ***, <i>P</i> ≤ 0.0001; ****, <i>P</i> ≤ 0.0001. Ctrl, control; dLN, tumor-draining lymph node.</p>