Tumor–macrophage interaction pathways

Tumor–macrophage interaction pathways refer to the complex network of signaling axes and molecular crosstalk between malignant cells and tumor-associated macrophages (TAMs) within the tumor microenvironment. These interactions are fundamental to cancer progression, as macrophages are often recruited and polarized by the tumor to promote immunosuppression, angiogenesis, and metastatic spread (Nature Reviews Drug Discovery, 2018). Key signaling axes include the CSF1/CSF1R pathway, which is critical for macrophage survival and differentiation, and the CD47/SIRPα "don't eat me" signal, which protects tumor cells from phagocytosis (PubMed: 31534003). Therapeutic strategies targeting these pathways aim to disrupt the pro-tumorigenic environment by depleting TAMs, blocking their infiltration via the CCL2/CCR2 axis, or reprogramming them into anti-tumor M1-like effectors using CD40 agonists or TLR ligands (PMC5461115). Several agents, such as the CSF1R inhibitor pexidartinib and various CD47-blocking antibodies, are in clinical use or development to harness the innate immune system against solid and hematological malignancies. Recent single-cell transcriptomic studies have further highlighted these pathways as key determinants of immune-enriched tumor subtypes, providing a basis for patient stratification in precision oncology (Gastroenteropancreatic neuroendocrine tumors in 2025).

Other names

Tumor-macrophage crosstalkTAM signaling pathwaysTumor-associated macrophage interaction axesTumor-TAM interaction

Therapeutic strategies targeting these pathways involve the inhibition of macrophage recruitment, the depletion of existing tumor-associated macrophages, or the reprogramming of immunosuppressive M2-like macrophages into pro-inflammatory M1-like phenotypes through the modulation of specific signaling axes such as CSF1/CSF1R, CD47/SIRPα, and CD40.