PD-L1 on Tumor-Derived Extracellular Vesicles Induces CD8⁺ T Cell Terminal Exhaustion and Mediates Anti-PD-1 Resistance in Head and Neck Squamous Cell Carcinoma.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) demonstrates suboptimal responses to current immune checkpoint inhibitors (ICIs), with objective response rates (ORRs) of merely 15-20%. The molecular mechanisms underlying these low ORRs remain incompletely defined. Here, two functionally distinct CD8⁺ T cell subsets are identified within the tumor microenvironment: precursor exhausted T (Tex^prog) cells and terminally exhausted T (Tex^term) cells. Notably, although anti-PD-1 therapy reduced Tex^prog cell frequencies, it failed to reverse Tex^term cells. Elevated Tex^term cell infiltration correlated with advanced tumor-node-metastasis (TNM) staging and poor prognosis. Furthermore, non-responders exhibited significantly higher baseline Tex

SUBMITTER: Fang R 

PROVIDER: S-EPMC12822461 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature