Increased level of PD1 and glycolysis in CD4 + T cell promote lymph node metastasis in OSCC patient

Background: Cervical lymph node metastasis is one of the poorest prognostic factors in oral squamous cell carcinoma (OSCC). Activated immune cells generally have metabolic abnormality in tumor microenvironment. However, it is unknown whether abnormal glycolysis in T cells could facilitate metastatic lymph nodes in OSCC patients. Methods Flow cytometry and immunofluorescence staining were used to analyze the differences in CD4 + PD1 + T cells between metastatic (LN+) and negative (LN-) lymph nodes. RT-PCR was performed to detail the expression of immune checkpoints and glycolysis-related enzymes in LN + and LN-. Results The frequency of CD4 + T cells decreased in LN+ ( p  = 0.0019). The PD1 expression of LN + increased markedly compared to that of LN- ( p  = 0.0205). Similarly, the PD1 of CD4 + T cells in LN + increased significantly compared to that of LN-. Moreover, glycolysis-related enzyme levels in CD4 + T cells from LN + were dramatically higher than those in LN-. Moreover, PD1 and Hk2 expressions in CD4 + T cells increased in LN + of OSCC patients with prior surgical treatment compared to those without. Conclusions These findings suggest that increased PD1 and glycolysis in CD4 + T cells may serve as pivotal regulators of OSCC metastatic lymph nodes, which are closely associated with elevated glycolysis.