C1QBP Drives M2 Macrophage Polarization Via TRAF2-CCL2 to Promote Oral Squamous Cell Carcinoma Progression

Oral squamous cell carcinoma (OSCC), frequently observed in the head and neck region, possesses mechanisms that have yet to be thoroughly clarified. Poor prognosis in OSCC is closely linked to the polarization of macrophages toward the M2 phenotype. Complement component 1q subcomponent-binding protein (C1QBP), a versatile protein commonly dysregulated in OSCC, has an unclear association with M2 macrophages.

Immunohistochemical (IHC) staining was conducted to determine the relationship between C1QBP expression and M2 macrophage infiltration. Flow cytometry (FC) and enzyme-linked immunosorbent assay (ELISA) were employed to explore the functional role of C1QBP in macrophages polarization. Furthermore, RNA sequencing combined with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) were utilized to verify the increased expression of TNF receptor-associated factor 2 (TRAF2) and C-C motif chemokine 2 (CCL2). Additional validation of these findings was performed through in vivo experiments.

A negative correlation was identified between C1QBP expression and CD206, a representative marker of M2 macrophages. Decreased levels of C1QBP in OSCC cells enhanced macrophage polarization toward the M2 phenotype and facilitated tumor progression by activating pivotal elements of the tumor necrosis factor (TNF) signaling pathway, notably TRAF2 and CCL2.

These findings suggest that C1QBP modulates the polarization of macrophages toward the M2 phenotype via the TRAF2-CCL2 signaling axis, thus contributing to OSCC malignancy progression. Consequently, targeting C1QBP to regulate M2 macrophage polarization may provide a promising therapeutic avenue for OSCC management.