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, H3K18la) and non-histone targets ( Strikingly, elevated histone Kla correlates with advanced tumor grade/stage and TME remodelingmanifested as increased immunosuppressive infiltrates (Tregs, M2 macrophages) and checkpoint molecule overexpression (PD-1, CTLA-4, LAG-3) ( 3.1 Macrophages Macrophages have exceptional phenotypic plasticity, dynamically transitioning between pro-inflammatory (M1) and reparative (M2) states in response to microenvironmental cues