Correlation Analysis Between IFIT2 and HLA Class II in Oral Cancer

Background/Aim: Interferon (IFN)-induced protein with tetratricopeptide repeats 2 (IFIT2) depletion is associated with tumor progression in oral cancer. The induction of human leukocyte antigen (HLA) class II molecules by IFN has also been reported in cancer cells. However, the correlation between IFIT2 and HLA class II in oral cancer remains unclear.

Materials and Methods: Xenograft and experimental metastasis animal models and cDNA microarray analysis were used to evaluate in vivo oral cancer progression. Western blotting and immunohistochemical staining were used to examine human leukocyte antigen (HLA) class II and IFIT2 protein levels in oral cancer cells and oral cancer patients.

Results: HLA class II genes exhibited increased expression in xenograft oral cancer sublines; however, no increases were detected in IFIT2-depleted xenograft and metastatic sublines, indicating that the loss of HLA class II expression may be related to IFIT2 depletion. In addition, IFIT2 may play a role in enhancing the responsiveness of oral cancer cells to IFN-γ-induced HLA class II expression. Clinically, IFIT2 protein expression is positively correlated with HLA class II protein expression in oral cancer. HLA class II expression was significantly negatively associated with lymph node metastasis compared with patients with negative HLA class II expression. Analysis of the TCGA database indicated that HLA class II expression, along with the enrichment of CD4⁺ T cells in the tumor microenvironment, may predict a better prognosis for patients with head and neck cancer, including oral cancer.

Conclusion: HLA class II expression may be positively correlated with IFIT2 expression in oral cancer cells. Clinically, low expression of HLA II molecules may be related to lymph node metastasis in oral cancer patients.