Domatinostat addition to checkpoint blockade controls growth of murine melanoma tumors through immune modulation.
(A) MeVa2.1.dOVA tumor volume across days of individual C57BL/6 mice treated with combinations of domatinostat, anti-PD-1, and anti-CTLA-4 or vehicle control (n = 15 mice per group; exception: vehicle control and triple combo treatment with n = 14 mice per group). (B) MeVa2.1.dOVA tumor volume across days of individual NSG mice treated with domatinostat or vehicle control (n = 13 mice per group). Dotted line indicates treatment duration. (C–F) Frequency of (C) CD8+ T cells, (D) CD4+ FoxP3+ Tregs, (E) CD206+, and (F) CD206– macrophages in the tumor, harvested after 13 d of treatment with domatinostat ± anti-PD-1 + anti-CTLA-4, as determined by flow cytometry analysis (n = 7–9 mice per group). Each dot represents tumor from one mouse. (G) Gene set enrichment analysis depicting Hallmark IFN-γ response, obtained using RNA sequencing analysis, in MeVa2.1.dOVA tumors after 13 d of treatment with domatinostat ± anti-PD-1 + anti-CTLA-4 (n = 4 mice per group). Statistical significance was estimated using one-way ANOVA followed by Sidak’s multiple comparisons test. Error bars represent SD. ns, not significant; **, P value < 0.01; ***, P value < 0.001; ****, P value < 0.0001.