Chronic ISG15 Exposure Accelerates CD8+ T-cell Dysfunction while Increasing PD-1 Blockade Sensitivity in Oral Squamous Cell Carcinoma.

ABSTRACT: Immunotherapy has emerged as a promising treatment for head and neck squamous cell carcinoma, yet clinical responses remain limited. Elevated expression of interferon-stimulated gene 15 (ISG15), commonly observed in oral squamous cell carcinoma (OSCC), may contribute to this limited efficacy. Although chronic interferon signaling is known to impair CD8+ T-cell function, the specific role of secreted ISG15 in T-cell exhaustion remains unclear. In this study, we report that the analysis of human OSCC datasets revealed significant enrichment of the ISG core score, including ISG15, in tumors compared with adjacent nontumor tissues. Using an in vitro model of human T-cell dysfunction, we found that acute ISG15 exposure enhanced CD8+ T-cell effector functions, whereas prolonged exposure induced

SUBMITTER: Chen YL 

PROVIDER: S-EPMC12755121 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature