Single-cell analysis of tumor microenvironment immune homeostasis and identification of prognostic biomarkers in head and neck squamous cell carcinoma.

BACKGROUNDHead and neck squamous cell carcinoma (HNSCC) is the eighth most common cancer globally, characterized by its diverse primary sites and immunosuppressive tumor microenvironment (TME). The TME impairs anti-tumor immunity, with T cells playing a critical role. However, T cells often become "exhausted," diminishing their anti-tumor function. Understanding the dynamic changes within the HNSCC TME is crucial for identifying therapeutic targets. To delineate immune homeostasis within the HNSCC TME at single-cell resolution and to identify robust prognostic biomarkers for patient risk stratification.

METHODSThis study utilized single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) to analyze the cellular composition and intercellular interactions in the HNSCC TME. We focused on the heterogeneity and differentiation trajectories of T cell subsets. Key genes involved in T-cell differentiation were identified and validated using data from The Cancer Genome Atlas-HNSCC (TCGA-HNSC) project. A prognostic risk model was constructed based on these genes.

RESULTSThe study revealed that the differentiation trajectory of T cells from naïve to exhausted states is regulated by genes such as CCL5, FOXP3, and NKG7. Six key genes (SERPINH1, PLAU, INHBA, TNFRSF4, CXCL13, and STAG3) were identified as prognostic biomarkers. High-risk genes (SERPINH1, PLAU, INHBA) correlated with tumor invasiveness, while low-risk genes (TNFRSF4, CXCL13, STAG3) were associated with improved prognosis. The prognostic risk model, based on these genes, achieved an area under the curve (AUC) of 0.66 for predicting 3-year survival.

CONCLUSIONSThis study provides valuable insights into the immune dynamics of HNSCC and identifies a prognostic risk model based on key immune-related genes, aiding in personalized treatment strategies. The findings offer a novel approach for precise prognostic evaluation and targeted therapy development in HNSCC, advancing clinical management and patient outcomes.