Figure 6 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>The antitumor efficacy of OX40/CD137 dual agonism is partially dependent upon IFNγ production by Tregs and/or their lineage-instable progeny. <b>A,</b> PCR genotyping of CD8<sup>+</sup>, CD4<sup>+</sup> Foxp3-GFP<sup>−</sup> Tconv, and CD4<sup>+</sup> Foxp3-GFP<sup>+</sup> Tregs sorted from the spleens of mice with the indicated genotypes after treatment with tamoxifen. Tregs have cell-specific excision of IFNγ only in mice possessing both the <i>Ifng</i><sup>fl/fl</sup> and <i>Foxp3</i><sup>EGFP-Cre-ERT2</sup> alleles. <b>B,</b> Schema representing treatment schedule of tamoxifen and FS120m. <b>C,</b> Tumor measurements at indicated timepoints after MC38 implantation of <i>Ifng</i><sup>fl/fl</sup><i>Foxp3</i><sup>EGFP-Cre-ERT2</sup> mice and controls given the indicated treatment. <b>D,</b> Replicate measurements of IFNγ<sup>+</sup> cells in the indicated CD4<sup>+</sup> T-cell populations from the tumor. <b>E,</b> Percentages (top) and counts per gram (bottom) of the indicated cell types in the tumors of mice of the indicated genotypes given the specified treatment. Data were analyzed by two-way ANOVA with Tukey correction for multiple comparisons (<b>C</b>) and ordinary one-way ANOVA with Tukey correction for multiple comparisons (<b>D</b> and <b>E</b>). Bars and error are mean and SEM. *, <i>P</i> ≤ 0.05; **, <i>P</i> ≤ 0.01; ***, <i>P</i> ≤ 0.001. Ctrl, control.</p>