Fig. 7: Combined MEKi and HDACi treatment enhances cytotoxic T cell infiltration and tumor apoptosis in vivo. | Nature Communications

Fig. 7: Combined MEKi and HDACi treatment enhances cytotoxic T cell infiltration and tumor apoptosis in vivo.

From: Combined targeted and epigenetic-based therapy enhances antitumor immunity by stabilizing GATA6-dependent MHCI expression in pancreatic ductal adenocarcinoma

Fig. 7: Combined MEKi and HDACi treatment enhances cytotoxic T cell infiltration and tumor apoptosis in vivo.

IHC staining of a T cell marker CD8 and CD4, activated T cell marker PD1, cytotoxic T cell marker GzmB, and b apoptosis marker Cl casp3 in CKP tumors with designed treatments. The right panels show the percentage of respective positive cells out of the total cells in the whole tumorous tissues as quantified by Definiens software (n = 4 independent mice for Ctrl group, n = 4 independent mice for MEKi group, n = 6 independent mice for HDACi group, n = 7 independent mice for MEKi+HDACi group). Mean ± SD is shown. One-way ANOVA and Kruskal–Wallis test were used. c mIF staining of combinatory MEKi and HDACi-treated CKP mice showing increased GzmB+ and Cl casp3+ cells in high tumor MHCI+ expression areas (n = 7). d Co-expression analysis shows the percentage of Cl casp3+ tumor cells within MHCI+PanCK+ and MHCI−PanCK+ population (n = 7). The percentage of respective positive cells out of the total cells was quantified by HALO software. Statistical significance was calculated by two-tailed Wilcoxon matched-pairs signed rank test. e Computational spatial analysis shows higher number of GzmB+ cells in close proximity (<150 μM radical distance) of MHCI+ Cl casp3+ cells when compared to MHCI− Cl casp3+ cells (n = 7). Quantified by Halo software. Mean ± SD is shown. Statistical significance was calculated by unpaired two-tailed Mann–Whitney test. Ctrl: vehicle control; MEKi: refametinib; HDACi: domatinostat; MEKi+HDACi: refametinib + domatinostat. Scale bar: μm.

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