Transcriptome combined with single-cell sequencing explored prognostic markers associated with T cell exhaustion characteristics in head and neck squamous carcinoma.

Head and neck squamous cell carcinoma (HNSC) ranks among the most prevalent cancers worldwide, characterized by significant heterogeneity and a complex immune microenvironment. T cell exhaustion is pivotal in the pathogenesis of HNSC, where depleted T cells exhibit reduced proliferative capacity and diminished effector function, facilitating tumor immune escape and subsequent disease progression. A thorough understanding of the primary mechanisms driving T cell depletion within the tumor microenvironment is essential for enhancing the efficacy of immunotherapeutic approaches in HNSC, with profound implications for patient outcomes. In this study, a single-cell atlas of HNSC was constructed, enabling an in-depth analysis of T cell heterogeneity. The differentiation trajectory of T cells, transitioning from normal tissue to HNSC, was characterized, revealing a predisposition toward depletion in the C2 T cell subgroup. A subsequent cross-analysis of significantly upregulated differentially expressed genes in the C2 T cell subset identified five characteristics pertinent to T cell C2, which informed the development of a clinical prognostic model. Additionally, maximum half inhibitory concentration (IC