Fig. 7: Treg-specific KO of HIF-2α confers resistance to tumor growth.
From: HIF-2α is indispensable for regulatory T cell function
a Treg-conditional deletion of Hif2a inhibits MC38 growth. MC38 colon adenocarcinoma cells (1 × 105) were subcutaneously inoculated into WT (Foxp3Cre) or Foxp3CreHif2af/f mice, with Foxp3Cre being littermate controls of Foxp3CreHif2af/f mice. Tumor growth was assessed every 2 days. Plotted values represent the mean and SEM of mice with a tumor. Numbers in brackets of legend represent tumor-free mice in each group. Red circle, Foxp3Cre (n = 7), blue square, Foxp3CreHif2af/f (n = 8). ****P < 0.0001. b–d Foxp3CreHif2af/f mice are resistant to B16F10 metastases. B16F10 melanoma cells (2 × 105) were intravenously administered into Foxp3Cre and Foxp3CreHif2af/f mice, with Foxp3Cre mice being littermates of Foxp3CreHif2af/f mice. At day 12 post-implantation, lungs were isolated b and the numbers of black nodules in lungs were quantified c. Red circle, Foxp3Cre (n = 7), blue square, Foxp3CreHif2af/f (n = 6) c. **P = 0.0082. Lung metastases were examined by H&E staining d. Bar indicates 100 μm. e Inhibition of MC38 growth by HIF-2α-downregulated Treg cells. Upper panel shows experimental setup. C57BL/6 male mice (6–8 weeks-old) were transplanted with 5 × 105 MC38 cells after 2 Gy irradiation on day 0. PBS, iTreg cells (1 × 106), or iTreg cells treated with PT2385 were adoptively transferred into MC38-bearing mice on days 3, 6, and 10. Tumor growth was assessed and is represented as mean tumor volume ± SEM. Black circle, PBS (n = 7); red circle, iTreg (n = 8); blue square, PT2385-treated iTreg (n = 7). ****P < 0.0001. P-value was determined by repeat measures two-way ANOVA with Tukey’s multiple comparisons test, with the Greenhouse-Geisser correction a, e or two-tailed unpaired t-test (c). Source data are provided as a Source data file.
