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Fig. 8 | Molecular Cancer

Fig. 8

From: Remodeling of the tumor microenvironment via disrupting Blimp1+ effector Treg activity augments response to anti-PD-1 blockade

Fig. 8

Deletion of Blimp1 in Treg cells remodels the TME and sensitizes the tumors to anti-PD-1 treatment. a-d) B16-OVA model was established as in Fig. 2c. a-b) CD45 cells were sorted and subject to NanoString analysis. a) DEGs related to angiogenesis and type 1 IFN signature (≥ 1.5 fold change and P < 0.05) in Foxp3YFP-Cre (WT) (n = 3) and Prdm1fl/flFoxp3YFP-Cre (KO) mice (n = 2). b) Reactome pathway analysis of DEGs revealed in a via NetworkAnalyst. c) IF staining of CD31 in the tumor and quantitation of CD31+ structures. Each dot represents the counted numbers within a field of view (160 ×). WT: n = 11 views from 6 mice; KO: n = 13 views from 6 mice. d) Expression and quantitation of MFI for MHCII and CD74 and percent Ki-67 of CD45 cells (WT: n = 3; KO: n = 4). e) Mice (WT + Ctrl, WT + a-PD-1, KO + a-PD-1: n = 5; KO + Ctrl: n = 4) were inoculated with B16-OVA (as in Fig. 2c) and treated with a-PD-1 or isotype control (Ctrl) Ab at days 3,6,9 post-implantation. Tumor volumes are shown. Upper, each dot represents an average of tumor volumes at a single day. Bottom, individual mouse at each day. WT: Foxp3YFP-Cre, KO: Prdm1fl/flFoxp3YFP-Cre. ns, no significance, * P < 0.05, ** P < 0.01 and *** P < 0.001 (c-d, e (upper), unpaired two-tailed Student’s t-test; e (bottom), two-way ANOVA with Tukey’s comparisons test, Day 20: **, WT + Ctrl vs. WT + a-PD-1; *, WT + Ctrl vs. KO + Ctrl; *, WT + Ctrl vs. KO + a-PD-1. Day 21: **, WT + Ctrl vs. WT + a-PD-1; *, WT + Ctrl vs. KO + Ctrl; **, WT + Ctrl vs. KO + a-PD-1. Day 26: **, WT + Ctrl vs. WT + a-PD-1; **, WT + Ctrl vs. KO + Ctrl; ****, WT + Ctrl vs. KO + a-PD-1. Day 28: *, WT + a-PD-1 vs. KO + Ctrl; ***, WT + a-PD-1 vs. KO + a-PD-1). Bars, mean ± SEM

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