Analysis of Head and Neck Cancer scRNA-seq Data Identified PRDM6 Promotes Tumor Progression by Modulating Immune Gene Expression

Zhenyu WuThurbu Tshering LepchaDawei ZhouMichele HeGuillaume Nicolas FichesYoungmin ParkJInshan HeChen JianwenKASN ShanakaSteve OghumuWeiqiang ZhaoAnjun MaQin MaJian Zhu^*Netty Santoso^*

• The Ohio State University, Columbus, United States

Head and neck squamous cell carcinoma (HNSCC) is a biologically aggressive and heterogeneous group of cancers with limited treatment options for patients who do not respond to standard therapies. While HPV-related HNSCCs tend to show better therapeutic outcomes, we still had limited understanding of the immune mechanisms underlying these cancers. Immuneresponsive genes (IRGs) have emerged as critical factors in regulating both tumor progression and immune response. Recent advances in single-cell RNA sequencing (scRNA-seq) and the development of cell-type specific regulon inference tools, such as IRIS3, have provided new insights into the tumor immune microenvironment. In this study, we leveraged the IRIS3 platform to analyze scRNA-seq data from HNSCC patient samples, identifying novel transcription factor (TF)-IRG networks that contribute to tumor proliferation and immune escape. Specifically, we identified PRDM6, a histone methyltransferase, possesses the previously unknown role in promoting tumor cell proliferation by inducing IRG expression. We further demonstrated that HPV viral oncoproteins (E6/E7) oncoproteins up-regulate the PRDM6 expression, which associates PRDM6 with HPV-positive HNSCC.