TLR2 Overexpression is Associated With an M1-Like Phenotypic Shift in M2-Like Macrophages and Reduced Nasopharyngeal Carcinoma Cell Growth

BACKGROUND: Nasopharyngeal carcinoma (NPC) has a poor prognosis due to an immunosuppressive tumor microenvironment dominated by M2-polarized tumor-associated macrophages. This study investigated the role of Toll-like receptor 2 (TLR2) in macrophage polarization and its impact on NPC. METHODS: THP-1-derived macrophages were polarized into M1 and M2 phenotypes, and TLR2 expression was compared. TLR2 was overexpressed in M2 macrophages, and conditioned media were used to treat NPC cells. Proliferation, migration, apoptosis, and EMT were assessed in vitro. Tumor growth was evaluated in a HONE-1 xenograft model co-injected with TLR2-overexpressing M2 macrophages. RESULTS: TLR2 was elevated in M1 but low in M2 macrophages. TLR2 overexpression in M2 macrophages was associated with an M1-like shift, with increased IL-1β, IL-6, and TNF-α and decreased IL-10, TGF-β, and CCL17. Conditioned media reduced NPC proliferation and migration, increased apoptosis, and reversed EMT markers. In vivo, co-injection reduced tumor growth. CONCLUSION: In the current experimental system, TLR2 overexpression is associated with an M1-like shift in M2 macrophages and reduced NPC progression, warranting further investigation as a potential immunomodulatory strategy.