Figure 1.Adaptor protein–mediated signaling pathways regulating macrophage polarization within the tumor microenvironmentSchematic representation illustrating how adaptor proteins integrate receptor-mediated signaling pathways to affect macrophage functional states within the TME. Tumor-derived ligands and danger-associated molecular patterns activate multiple receptors on macrophages, including pattern recognition receptors (PRRs), TLR2/4, TREM, IL-4R, and IL-6R, etc. Upon receptor activation, adaptor proteins transmit signals to downstream pathways including NF-κB, TBK1–IRF3/7, MAPK (MEK/ERK), PI3K–Akt, mTORC1, and JAK–STAT signaling. Collectively, adaptor proteins act as critical molecular scaffolds that integrate signals from the TME to determine macrophage polarization toward anti-tumor or pro-tumor phenotypes, ultimately influencing tumor immunity and cancer progression.
