Sphingosine kinase 1 promotes tumor immune evasion by regulating the MTA3-PD-L1 axis.

ABSTRACT: Immune checkpoint blockade (ICB) exhibits considerable benefits in malignancies, but its overall response rate is limited. Previous studies have shown that sphingosine kinases (SPHKs) are critical in the tumor microenvironment (TME), but their role in immunotherapy is unclear. We performed integrative analyses including bioinformatics analysis, functional study, and clinical validation to investigate the role of SPHK1 in tumor immunity. Functionally, we demonstrated that the inhibition of SPHK1 significantly suppressed tumor growth by promoting antitumor immunity in immunocompetent melanoma mouse models and tumor T-cell cocultures. A mechanistic analysis revealed that MTA3 functions as the downstream target of SPHK1 in transcriptionally regulating tumor PD-L1. Preclinically, we found that

SUBMITTER: Lau P 

PROVIDER: S-EPMC9508236 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature