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Updated: Jan 7, 2026

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RUVBL1によるmTORC1活性化は、口腔扁平上皮癌の腫瘍進行と免疫逃避を駆動する

Xinpei Wang¹, Zuxuan Zhao², Fengyang Jing³

¹Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China; Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, China; Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences, Beijing, 100081, China.

|December 27, 2025

要旨

Background And Aims:

Oral squamous cell carcinoma (OSCC) is a prevalent head and neck malignancy for which surgical resection remains the primary therapeutic approach. Although immunotherapy, particularly immune checkpoint blockade targeting PD-1/PD-L1, has been revolutionary, only a small number of patients with OSCC have clinically benefited from it. Therefore, elucidating the molecular mechanisms underlying OSCC progression and immune evasion is crucial. RuvB-like AAA ATPase 1 (RUVBL1) has been implicated in diverse biological processes and modulates tumour immunity. Little is known regarding the function of RUVBL1 and its mechanism of action in OSCC. In this study, we aimed to understand RUVBL1 regulation in OSCC tissues and how expression correlates with patient prognosis.

Materials And Methods:

We conducted bioinformatics analysis, functional assays in vitro, co-culture experiments, and murine xenograft models, along with validation in clinical samples. To investigate the underlying mechanism, transcriptome sequencing and biochemical as well as molecular analyses were utilized.

Key Findings:

RUVBL1 promotes tumour growth and regulates the tumour microenvironment by controlling PD-L1 expression by targeting the rapamycin kinase (mTOR) pathway, thereby impairing both the infiltration and effector function of T cells in OSCC. Pharmacological inhibition of RUVBL1 with CB6644 suppressed tumour growth and synergised with PD-L1 blockade and conventional therapy. Collectively, these findings identify RUVBL1 as a critical driver of OSCC progression and immune modulation.

Significance:

Our findings highlight the potential of RUVBL1 as a prognostic biomarker and therapeutic target to enhance treatment efficacy.

キーワード:

CB6644 免疫チェックポイント阻害口腔扁平上皮癌 PD-L1 RUVBL1

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