Association between APOBEC3H-Mediated Demethylation and Immune Landscape in Head and Neck Squamous Carcinoma

الملخص EN

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.