Pro-inflammatory cytokine production in M2-like tumor-associated macrophages

Pro-inflammatory cytokine production in M2-like tumor-associated macrophages (TAMs) is a biological process and therapeutic strategy aimed at reversing the immunosuppressive environment of a tumor. In many cancers, TAMs adopt an M2-like phenotype, which is characterized by the production of anti-inflammatory cytokines (e.g., IL-10, TGF-beta) and the promotion of tissue repair, angiogenesis, and tumor progression (Mantovani et al., 2017, Nature Reviews Clinical Oncology). By stimulating these cells to produce pro-inflammatory cytokines such as Interleukin-12 (IL-12) and Tumor Necrosis Factor-alpha (TNF-alpha), researchers aim to repolarize them into an M1-like phenotype that actively recruits and activates cytotoxic T cells and Natural Killer (NK) cells to destroy malignant cells (Cassetta & Pollard, 2018, Nature Reviews Drug Discovery). This shift is often pursued using agonists of Toll-like receptors (TLRs) or inhibitors of specific signaling nodes like PI3K-gamma or CSF1R (Pathria et al., 2019, Science). While this approach holds significant potential for enhancing the efficacy of checkpoint inhibitors, it also poses risks of systemic inflammation and cytokine release syndrome if the activation is not sufficiently localized to the tumor microenvironment.

Other names

TAM repolarizationM2-to-M1 macrophage polarizationMacrophage reprogrammingInduction of pro-inflammatory cytokines in tumor-associated macrophages

Induction of a phenotypic shift in tumor-associated macrophages from an immunosuppressive M2-like state to a pro-inflammatory M1-like state to stimulate anti-tumor immunity.