Programmed death-ligand 1 regulates ameloblastoma growth and recurrence.
10.1038/s41368-025-00364-w
- Author:
Linzhou ZHANG
1
;
Hao LIN
1
;
Jiajie LIANG
1
;
Xuanhao LIU
1
;
Chenxi ZHANG
1
;
Qiwen MAN
1
;
Ruifang LI
1
;
Yi ZHAO
2
;
Bing LIU
3
Author Information
1. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
2. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. zhao_yi@whu.edu.cn.
3. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. liubing9909@whu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Ameloblastoma/metabolism*;
Humans;
B7-H1 Antigen/metabolism*;
Neoplasm Recurrence, Local/pathology*;
Signal Transduction;
Cell Proliferation;
Up-Regulation;
TOR Serine-Threonine Kinases/metabolism*;
Proto-Oncogene Proteins c-akt/metabolism*;
Telomerase/metabolism*;
Jaw Neoplasms/metabolism*;
Epithelial-Mesenchymal Transition;
Animals;
Cell Line, Tumor;
Female;
Male
- From:
International Journal of Oral Science
2025;17(1):29-29
- CountryChina
- Language:English
-
Abstract:
Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT+-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT+-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
