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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Association between APOBEC3H-Mediated Demethylation and Immune Landscape in Head and Neck Squamous Carcinoma
Qin Liu1, Yue-Wen Luo2, Ruo-Yan Cao1
1Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, China.
Abstract:
Immunotherapy has been demonstrated as a promising strategy in controlling head and neck squamous cell carcinoma (HNSC). The AID/APOBEC family is well characterized as DNA mutator and considered to play critical roles in immune responses in HNSC. However, the expression pattern and deamination-dependent demethylation roles of AID/APOBECs in HNSC are unclear. In this study, the RNA-seq and DNA methylation profiles of HNSC from TCGA database and cell-based experiments were applied to analyze the relationships between AID/APOBEC expression levels, patients' clinical outcomes, methylation alterations, and immune responses. Here, we found that APOBEC3H was abnormally upregulated in HNSC patients. HPV+ patients tended to have higher APOBEC3H levels than HPV- patients. Remarkably, patients with high APOBEC3H levels showed a favorable overall survival. Furthermore, tumors with high APOBEC3H levels exhibited a genome-wide DNA hypomethylation pattern. APOBEC3H was identified to demethylate and upregulate CXCL10 and improve CD8+ T cell tumor infiltration in the tumor microenvironment. Collectively, APOBEC3H plays critical roles in CD8+ T cell immune infiltration and activation in HNSC, which may be a potential biomarker for oncoimmunotherapy in HNSC.
Insights
High APOBEC3H levels in head and neck squamous cell carcinoma (HNSC) correlate with improved survival and increased CD8+ T cell infiltration. This suggests APOBEC3H may be a valuable biomarker for immunotherapy in HNSC patients.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Immunotherapy shows promise for head and neck squamous cell carcinoma (HNSC).
- The AID/APOBEC family's role in HNSC immune response and DNA methylation is not fully understood.
- Clarifying AID/APOBEC expression and function is crucial for HNSC treatment strategies.
Purpose of the Study:
- To investigate the expression patterns of AID/APOBEC family members in HNSC.
- To analyze the relationship between AID/APOBEC expression, DNA methylation, and immune responses in HNSC.
- To determine the clinical significance of APOBEC3H in HNSC prognosis and immunotherapy.
Main Methods:
- Utilized RNA-sequencing and DNA methylation profiling data from The Cancer Genome Atlas (TCGA) database.
- Conducted cell-based experiments to validate findings.
- Analyzed correlations between AID/APOBEC expression, clinical outcomes, methylation status, and immune cell infiltration.
Main Results:
- APOBEC3H was significantly upregulated in HNSC, particularly in HPV+ patients.
- Higher APOBEC3H expression was associated with favorable overall survival in HNSC patients.
- Tumors with high APOBEC3H levels displayed genome-wide DNA hypomethylation and increased CXCL10 expression.
- APOBEC3H promoted CD8+ T cell infiltration and activation within the tumor microenvironment.
Conclusions:
- APOBEC3H plays a critical role in enhancing CD8+ T cell immune infiltration and activation in HNSC.
- APOBEC3H-mediated demethylation of CXCL10 contributes to its anti-tumor effects.
- APOBEC3H represents a potential predictive biomarker for oncoimmunotherapy in head and neck squamous cell carcinoma.
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