Fig. 6. CD25 engagement by therapeutic IL-2 is crucial for the efficacy of PD-1 + IL-2 combination therapy.

a, LCMV chronically infected mice (> 40 days after infection) were left untreated, or were treated with anti-PD-L1 antibodies, anti-PD-L1 plus IL-2 (WT), or anti-PD-L1 plus IL-2(V) (modified IL-2 with abolished CD25 binding) for 2 weeks. The colour key in a applies to b–d and f. b, LCMV-specific CD8⁺ T cell responses. The numbers of LCMV-specific D^bGP33⁺ CD8⁺ T cells in the indicated tissues after the various treatments are shown. c, The numbers of IFNγ⁺TNFα⁺ and IFNγ⁺IL-2⁺ LCMV-specific CD8⁺ T cells in the four groups. Spleen cells were stimulated with pools of LCMV-specific peptides for 5 h and analyzed by intracellular cytokine staining. d, e, LCMV-specific D^bGP33⁺ CD8⁺ T cells were sorted from spleens of LCMV chronically infected mice after various treatments and analyzed using RNA-seq. Naive CD44^low CD8⁺ T cells from uninfected mice are also included in the analysis. d, PCA plot for naive (CD44^low) and D^bGP33⁺ CD8⁺ T cells generated by the different treatments. e, The mean relative expression of key specific genes in D^bGP33⁺ CD8⁺ T cells generated after the various treatments. f, The viral titre in the indicated tissues in the four groups of mice. The results were pooled from 2–3 experiments with 2–3 mice per group in each experiment. Data are geometric mean ± 95% CI (b and c) or mean ± s.d. (f). P values are shown; statistical comparisons were performed using Kruskal-Wallis test with Dunn’s multiple comparison test (b and c) or one-way ANOVA with Tukey’s multiple comparison test (f).