SPHK1 promotes HNSCC immune evasion by regulating the MMP1-PD-L1 axis.

ABSTRACT: Rationale: Immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy against head and neck squamous cell carcinoma (HNSCC), but their overall response rate (ORR) remains limited. Previous studies have highlighted the crucial role of sphingosine kinases (SPHKs) in the tumor microenvironment (TME); however, their function in immunotherapy remains unclear. Methods: We conducted comprehensive bioinformatics analysis, functional studies, and clinical validation, to investigate the role of SPHK1 in the immunology of HNSCC. Results: Functionally, SPHK1 significantly promoted tumor growth by inhibiting anti-tumor immunity in immune-competent HNSCC mouse models and tumor-T cell co-cultures. Mechanistic analysis revealed that SPHK1 regulated matrix metalloprotei

SUBMITTER: Fang Q 

PROVIDER: S-EPMC11610131 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature