Epigenetic programming via lysine-specific demethylase 1 regulates responses to immune checkpoint blockade.

Immune checkpoint blockade has revolutionized cancer therapy, but durable benefit remains limited by immune-cold tumor states, poor antigen presentation, T cell exhaustion, and adaptive resistance. Recent studies position lysine-specific demethylase 1 (LSD1) as a druggable epigenetic regulator that links these barriers across tumor and immune cells. Emerging evidence shows that targeting LSD1 can restore major histocompatibility complex class I antigen presentation, activate viral mimicry and interferon programs, modulate programmed death-ligand 1 in a context-dependent manner, influence CD8+ T cell state transitions, and restrain tumor plasticity. In this review, we feature these mechanistic advances, compare evolving drug classes, and outline biomarker-guided strategies that may support the rational development of next-generation combination immunotherapy.