Adaptor proteins regulating tumor-associated macrophage polarization during cancer progression

Adaptor proteins serve as essential molecular scaffolds within the tumor microenvironment, linking activated receptors to downstream signaling pathways and coordinating the assembly of multiprotein complexes that modulate immune responses. Emerging evidence suggests that adaptor proteins play a critical role in shaping macrophage phenotypic plasticity. Tumor-associated macrophages exhibit functional heterogeneity and can adopt either anti-tumorigenic phenotypes that promote immune activation or pro-tumorigenic phenotypes that support tumor growth, metastasis, and immune evasion. The dynamic transition between these functional states is tightly controlled by intracellular signaling networks in which adaptor proteins function as key regulatory nodes. Based on available mechanistic studies, we systematically summarize adaptor molecules that govern signaling pathways driving macrophage polarization within the cancer condition. Additionally, this review underscores the significance of adaptor proteins as key modulators of macrophage phenotype and highlights their potential as therapeutic targets for reprogramming macrophages to enhance anti-tumor immunity. Collectively, we provide a conceptual framework for understanding adaptor-mediated immune regulation in cancer and support the development of targeted strategies to shape the tumor microenvironment.