Increased levels of PD1 and glycolysis in CD4+ T cells are positively associated with lymph node metastasis in OSCC

Kun Wu; Nannan Han; Yuanyuan Mao; Yan Li

doi:10.1186/s12903-023-03043-6

Increased levels of PD1 and glycolysis in CD4⁺ T cells are positively associated with lymph node metastasis in OSCC

BMC Oral Health. 2023 Jun 3;23(1):356. doi: 10.1186/s12903-023-03043-6.

Authors

Kun Wu^{1

2}, Nannan Han², Yuanyuan Mao^{3

4}, Yan Li^{5

6}

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Second Xiangya Hospital of Central South University, Changsha, China.
² Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Oral and Maxillofacial Surgery, Second Xiangya Hospital of Central South University, Changsha, China. maoyuanyuan@csu.edu.cn.
⁴ Department of Anesthesiology, Second Xiangya Hospital of Central South University, Renmin road, No. 139, Changsha, Hunan, 410011, China. maoyuanyuan@csu.edu.cn.
⁵ Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. liyan1106369@163.com.
⁶ Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. liyan1106369@163.com.

Abstract

Background: Cervical lymph node metastasis is one of the poorest prognostic factors in oral squamous cell carcinoma (OSCC). Activated immune cells generally have metabolic abnormalities in the tumour microenvironment. However, it is unknown whether abnormal glycolysis in T cells could facilitate metastatic lymph nodes in OSCC patients. The aim of this study was to investigate the effects of immune checkpoints in metastatic lymph nodes and determine the correlation between glycolysis and immune checkpoint expression in CD4⁺ T cells.

Methods: Flow cytometry and immunofluorescence staining were used to analyse the differences in CD4⁺ PD1⁺ T cells between metastatic lymph nodes (LN⁺) and negative lymph nodes (LN^-). 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⁺ patients (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^-. Additionally, glycolysis-related enzyme levels in CD4⁺ T cells from LN⁺ patients were dramatically higher than those in LN^- patients. PD1 and Hk2 expression in CD4⁺ T cells was also increased in LN⁺ OSCC patients with prior surgical treatment compared to those without.

Conclusions: These findings suggest that lymph node metastasis and recurrence in OSCC are associated with increases in PD1 and glycolysis in CD4⁺ T cells; this response may serve as a potential regulator of OSCC progression.

Keywords: CD4+ T cells; glycolysis; immune checkpoint; lymph node metastasis; oral squamous cell carcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD4-Positive T-Lymphocytes / metabolism
CD4-Positive T-Lymphocytes / pathology
Humans
Lymphatic Metastasis
Mouth Neoplasms* / pathology
Prognosis
Squamous Cell Carcinoma of Head and Neck* / pathology
Tumor Microenvironment