Polarization of tumor-associated macrophages and Gas6/Axl signaling in oral squamous cell carcinoma

• Activated Gas6/Axl signal of OSCC could polarize macrophages to M2 macrophage.
• Axl/Akt/NF-κb pathway of OSCC involved in regulating M2 macrophage polarization.
• In vivo study also confirmed Gas6/Axl signal of OSCC associated with M2 distribution.

SummaryBackgroundThis study investigated the potential involvement of Axl signaling in polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC).MethodsCondition medium (CM) from OSCC cells (OEC-M1 and YD38) were collected and their effects on macrophage (THP-1) polarization were examined. Modulation of Axl, PI3/Akt, and NF-κB were performed to investigate their potential involvement in TAM polarization. Expression of pAxl and CD206 were analyzed by immunohistochemistry in OSCC tissues.ResultsTHP-1 polarized to M2 phenotype with increasing expression of interleukins, vascular endothelial growth factor, matrix metalloproteinase and CD206 upon treatment with CM of OSCC. Activated Axl signaling in OSCC enhanced M2 induction ability. Suppression of Axl signaling and inhibition of PI3/Akt and NF-κB diminished M2 induction. pAxl expression was significantly associated with distribution of CD206 positive cells in OSCC tissues.ConclusionAxl signaling of OSCC involved in polarizing TAMs toward M2 phenotype. Induction of M2 phenotype macrophage polarization by OSCC cells might involve the Axl/PI3/Akt/NF-κB pathway.