Fig. 4

In CTL-high C38 tumors, domatinostat treatment results in activated effector CTL populations expressing PD-1/LAG3. C38 tumor fragments were inoculated s.c. into C57BL/6 J mice; when tumor volumes reached 150 mm³, animals were treated with 20 mg/kg domatinostat or vehicle twice daily; tumors were harvested for analysis of cell populations by flow cytometry after 9 (c-h, n = 6) or 18 treatment days (a, b, n = 10). a, MHC class I and II expression on tumor cells (CD45⁻). b, MHC class II expression on M1 macrophages (CD45⁺CD3⁻CD11b⁺CD38⁺). c, Proportion of CTLs (CD3⁺CD8⁺) within tumors. d-h, Characterization of intratumoral CTLs: proportions of the effector memory (EM, CD44⁺CD62L⁻) (d), CD69⁺ and GITR⁺ (e), PD-1⁺, LAG3⁺ and PD-1⁺/LAG3⁺ double-positive (DP) (f) and Ki67⁺ CTLs (g) and of Ki67⁺ cells within the PD-1⁺/LAG3⁺ CTL population (h). a-c, g, h, Mean ± SD showing all data points; gMFI, geometric mean fluorescence intensity. d-f, Mean + SD shown in stacked bars. P-value: Mann-Whitney test, two-tailed. *, P < 0.05; **, P < 0.01