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Updated: Sep 2, 2025
Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Inhibition of DNMT1 potentiates antitumor immunity in oral squamous cell carcinoma
Shao-Chen Yang1, Wu-Yin Wang1, Jun-Jie Zhou1
1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 430079 Wuhan, China.
Abstract:
Epigenetic alterations, including DNA methylation, play crucial roles in the tumor. Epigenetic drugs like DNA methyltransferase-1 (DNMT1) inhibitors have been exhibited positive effects in cancer treatment. However, the role of DNMT1 in oral squamous cell carcinoma (OSCC) is less clearly described. What is more, the effects on the immune microenvironment of DNMT1 have not become appreciated. In this research, we determine the expression levels of DNMT1 and the association of prognosis by analyzing human OSCC tissue microarrays. Two different types of immunocompetent mouse OSCC models were established to explore the effects of DNMT1 inhibitor on the tumor microenvironment(TME). We identified DNMT1 was highly expressed both in human and mouse OSCC tissues. The expression levels of DNMT1 was also correlated with the immunosuppressive molecules and tumor-promoter such as VISTA, PD-L1, B7-H4, and PAK2, indicating a worse prognosis. Of particular concern is that DNMT1 inhibition improved TME and delayed tumor growth by decreasing myeloid-derived suppressor cells (MDSCs) and increasing tumor-infiltrating T cells. Our data suggests that DNMT1 play a key role in OSCC and has a possible immunotherapeutic marker treatment.
Insights
DNA methyltransferase-1 (DNMT1) is highly expressed in oral squamous cell carcinoma (OSCC), correlating with poor prognosis. DNMT1 inhibition improved the tumor immune microenvironment and delayed tumor growth in preclinical models.
Area of Science:
- Oncology
- Immunology
- Epigenetics
Background:
- Epigenetic alterations, including DNA methylation, are vital in cancer development.
- DNA methyltransferase-1 (DNMT1) inhibitors show promise in cancer therapy, but their role in oral squamous cell carcinoma (OSCC) and impact on the immune microenvironment remain unclear.
Purpose of the Study:
- To investigate the expression of DNMT1 in OSCC and its prognostic significance.
- To explore the effects of DNMT1 inhibition on the tumor immune microenvironment (TME) in OSCC models.
Main Methods:
- Analysis of DNMT1 expression in human OSCC tissue microarrays.
- Utilizing immunocompetent mouse OSCC models to study DNMT1 inhibitor effects on the TME.
Main Results:
- DNMT1 was significantly upregulated in both human and mouse OSCC tissues.
- High DNMT1 expression correlated with immunosuppressive molecules (VISTA, PD-L1, B7-H4) and tumor promoters (PAK2), indicating a worse prognosis.
- DNMT1 inhibition reduced myeloid-derived suppressor cells (MDSCs) and increased tumor-infiltrating T cells, thereby improving the TME and delaying tumor growth.
Conclusions:
- DNMT1 plays a critical role in OSCC progression and immune evasion.
- DNMT1 inhibition demonstrates potential as an immunotherapeutic strategy for OSCC.
