Monocyte/macrophage-mediated trained immunity in disease prevention and immunotherapy

Trained immunity refers to a functional reprogramming of the innate immune system that enhances its ability to respond to secondary stimuli. Monocytes and macrophages are central effectors of innate immunity with broad therapeutic relevance. Their capacity to acquire trained immunity enhances host defense and shapes immune homeostasis through epigenetic, metabolic, and functional changes. Unlike previous reviews that primarily focus on molecular mechanisms or vaccine-induced training, this review emphasizes the distinct roles of monocyte/macrophage-mediated trained immunity, originating from both central and peripheral sources. We further discuss how nanomaterials can be harnessed to precisely modulate this process, offering new opportunities for infection control, tumor immunotherapy, and the regulation of chronic inflammatory diseases. This dual-perspective framework provides a foundation for translating trained immunity into targeted clinical interventions. • Central and peripheral trained immunity affects infection, inflammation and cancer. • It reprograms innate cells via lasting epigenetic and metabolic changes throughout the body. • Nanomaterials enable targeted delivery and precise control for advanced immunotherapy applications.