Conclusion
Our results indicate that TANs can serve as a prognostic biomarker and ALDH3A1 could be a promising therapeutic target for regulating TANs N2 polarization in antitumor therapy.
Methods
Immunohistochemistry and immunofluorescence were performed to investigate the abundance of TANs and the expression of ALDH3A1. dHL-60 were induced with tumor-conditioned media and recombinant IL-6/IL-8. The expression of key proteins in PI3K/AKT/NF-κB pathway were detected by RT-PCR and western blot. A xenograft model was utilized to examine the effect of ALDH3A1 on tumorigenicity and polarization of TANs.
Results
In patients with OSCC, TANs significantly increased and were associated with a worse prognosis. Additionally, ALDH3A1 negatively correlated with TANs infiltration and especially the N2 phenotype which was the prominent part in OSCC. Furthermore, our study demonstrated that tumor-derived IL-8 drives ALDH3A1-mediated TANs N2 polarization in the TME through PI3K/AKT/NF-κB pathway in vitro and in vivo.