(A) Single cell suspensions of PTEN/p53-deficient prostate GEM tumors were treated with copanlisib (C, 100 nM), trametinib (T, 5 nM) or their combination for 24 hours, and conditioned media (CM) was collected at the end of treatment. FACS-sorted TAM were incubated ex vivo in CM for 24 hours, followed by co-culture with CTV dye stained-AC1/SC1 cells for 2 hours. Bar graphs demonstrate histone lactylation status (B) and phagocytic activity (C) of MHC-IIhi/PD-1hi/lo expressing TAM, relative to untreated group. FC = fold change. n=2 independent biological experiments. Significances/p-values were calculated by one-way ANOVA and indicated as follows, *p<0.05, **p<0.01 and ***p<0.001.