M1-like macrophage (M1 macrophage)

M1-like macrophages, often termed classically activated macrophages, represent a pro-inflammatory state of the macrophage lineage triggered primarily by Th1 cytokines like interferon-gamma (IFN-γ) or microbial products such as lipopolysaccharide (LPS) (Yunna et al., Front Cell Dev Biol, 2020 [PMID: 32671064]). These cells serve as a primary defense mechanism, utilizing high levels of nitric oxide (NO) and reactive oxygen species (ROS) to mediate the killing of intracellular pathogens and tumor cells. In the tumor microenvironment, M1-like macrophages are generally considered beneficial due to their ability to present antigens, secrete pro-inflammatory cytokines like IL-12 and TNF-α, and promote a robust Th1-mediated immune response (Cassetta & Pollard, Nature Reviews Drug Discovery, 2018 [PMID: 29541815]). Conversely, their overactivation is a hallmark of chronic inflammatory and autoimmune diseases, where they contribute to persistent tissue injury and fibrosis. Current drug development efforts focus on 'macrophage repolarization,' seeking to switch suppressive M2-like macrophages toward an M1-like phenotype to overcome immune evasion in oncology, or conversely, to limit M1 activity in autoimmune contexts.

Other names

Classically activated macrophagePro-inflammatory macrophageM1 phenotypeM1-polarized macrophage

M1-like macrophages are induced via TLR signaling (e.g., LPS) and IFN-gamma to produce pro-inflammatory cytokines (TNF-alpha, IL-12, IL-6), reactive oxygen species (ROS), and nitric oxide (NO) via iNOS to destroy pathogens or tumor cells (Murray et al., Immunity, 2014 [PMID: 24922590]). Therapeutic strategies aim to repolarize immunosuppressive M2 macrophages into the M1 phenotype using PI3K-gamma inhibitors or CD40 agonists to enhance anti-tumor immunity (Mantovani et al., Nature Reviews Immunology, 2017 [PMID: 28930239]).