Synergistic effect on disease outcome in a preclinical LCH model with combined PD-1 blockade and targeted MAPK inhibition. (A) Treatment and evaluation schema for intervention with anti-MEKi, -PD-L1, and/or -PD-1 blocking antibodies. (B-D) Organ weight of lung (B), liver (C), and spleen (D) from BRAFV600E^CD11c mice treated with the different combinations indicated. (E, F) Hematoxylin and eosin–stained lung (E) and liver (F) specimens from BRAFV600E^CD11c mice after the indicated treatment regimens compared with the corresponding control groups. The disease burden significantly decreased in lung and liver of BRAFV600E^CD11c mice cotreated with MEKi and anti-PD-1 compared with the other regimens (G). (H-J) FlowSOM minimal spanning tree (MST) plots of lymphoid (top) and myeloid (bottom) cells from representative lesion biopsy specimens of lung of BRAFV600E^CD11c mice in isotype+vehicle MEKi (H), anti-PD-L1+MEKi (I), and anti-PD-1+MEKi (J) groups. For panels B-D and G, data are the means ± SD (n = 9 mice per group). *P < .05; ***P < .001, ****P < .0001, ns, not significant (P > .05), by 1-way ANOVA with Tukey’s post hoc test.