Increased PD1 and Glycolysis in CD4+ T Cell Promotes Lymph Node Metastasis in Oral Squamous Cell Carcinoma Patients

Abstract

Background: The presence of cervical lymph node metastasis is one of the poorest prognostic factors in oral squamous cell carcinoma (OSCC) with 50% reduction in survival of patients with lymph node positive involvement compared to those without. However, it is unknown whether immune checkpoint contributed to metastatic lymph nodes in OSCC patients. Results: We found that frequency of CD4+ T cells decreased in metastatic lymph nodes (p = 0.0019). In following experiments, immune checkpoints (PD1, PDL1 and CTLA4) of CD4+ T cells were detected in metastatic lymph node (LN+) and paired negative lymph node (LN-) of OSCC patients. The PD1 expression of LN+ was increased markedly compared to LN- (p = 0.0205). Similarly, the PD1 of CD4+ T cells in LN+ was increased significantly compared to LN-. We also found that glycolysis related enzymes levels in CD4+ T cells from LN+ were elevated dramatically compared to LN-. Moreover, PD1 and Hk2 expression of CD4+ T cells was increased in metastatic lymph nodes of OSCC patients with prior surgical treatment compared to those without. Conclusions: These findings suggested that increased PD1 and glycolysis in CD4+ T cell may serve as a pivotal regulator of OSCC metastatic lymph nodes via elevating glycolysis related enzymes level, especially in Hk2.