Classically activated macrophage (M1 macrophage) (M1)

Classically activated macrophages, or M1 macrophages, represent a pro-inflammatory phenotype of the innate immune system characterized by high microbicidal and tumoricidal activity. They are typically induced by Th1-type cytokines such as interferon-gamma (IFN-γ) and microbial components like lipopolysaccharide (LPS), signaling primarily through the JAK-STAT1 and NF-κB pathways (6, 12). Once activated, M1 macrophages produce reactive oxygen and nitrogen species (ROS/RNS) and secrete pro-inflammatory cytokines, including TNF-α, IL-12, and IL-1β, to destroy pathogens and eliminate malignant cells (1, 14). In the context of oncology, therapeutic efforts focus on repolarizing immunosuppressive M2-like tumor-associated macrophages into the M1 phenotype to enhance anti-tumor immunity (2, 5). However, dysregulated or chronic M1 activation is a major driver of tissue damage in autoimmune diseases, atherosclerosis, and neurodegeneration (11, 15). Consequently, M1 macrophages serve as a central target for both induction in cancer immunotherapy and inhibition in chronic inflammatory conditions (9, 13).

Other names

Classically activated macrophagePro-inflammatory macrophageM1-polarized macrophageKiller macrophageCAM

Phenotypic repolarization from M2 to M1; Activation of JAK-STAT1 and NF-kB signaling pathways; Induction of pro-inflammatory cytokine secretion; Enhancement of antibody-dependent cellular phagocytosis (ADCP) and antigen presentation.