Depletion of PHLDB2 Suppresses Epithelial–Mesenchymal Transition and Enhances Anti-Tumor Immunity in Head and Neck Squamous Cell Carcinoma
Hongyu Li,
Ziyi Wang,
Huiting Liang,
Xiaoyong Liu,
Haichao Liu,
Zehang Zhuang,
Jinsong Hou
Affiliations
Hongyu Li
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, 56 Lingyuan Road West, Guangzhou 510055, China
Ziyi Wang
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, 56 Lingyuan Road West, Guangzhou 510055, China
Huiting Liang
Department of Stomatology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
Xiaoyong Liu
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, 56 Lingyuan Road West, Guangzhou 510055, China
Haichao Liu
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, 56 Lingyuan Road West, Guangzhou 510055, China
Zehang Zhuang
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, 56 Lingyuan Road West, Guangzhou 510055, China
Jinsong Hou
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, 56 Lingyuan Road West, Guangzhou 510055, China
The role of Pleckstrin homology-like domain family B member 2 (PHLDB2) in the regulation of cell migration has been extensively studied. However, the exploration of PHLDB2 in head and neck squamous cell carcinoma (HNSCC) is still limited in terms of expression, function, and therapeutic potential. In this study, we discovered an upregulation of PHLDB2 expression in HNSCC tissues which was correlated with a negative prognosis in patients with HNSCC. Additionally, we determined that a high level of expression of PHLDB2 is crucial for maintaining cell migration through the regulation of the epithelial–mesenchymal transition (EMT). Furthermore, we demonstrated that the ablation of PHLDB2 in tumor cells inhibited tumorigenicity in a C3H syngeneic tumor-bearing mouse model. Mechanistically, PHLDB2 was found to be involved in the regulation of T cell anti-tumor immunity, primarily by enhancing the activation and infiltration of CD8+ T cells. In light of these findings, PHLDB2 emerges as a promising biomarker and therapeutic target for interventions in HNSCC.
