Soluble NKG2D ligands impair CD8⁺ T cell antitumor function dependent of NKG2D downregulation in neuroblastoma.

ABSTRACT: T cell-based immunotherapy has achieved remarkable beneficial clinical outcomes. Tumor-derived NKG2D ligands (NKG2DL) allow tumors to escape immunologic surveillance. However, the mechanism underlying NKG2DL-mediated immune escape in neuroblastoma (NB) remains incompletely understood. In the present study, first soluble NKG2DL, soluble major histocompatibility complex (MHC) class-I-related chain A and soluble UL-16 binding proteins expression levels were determined in both the serum from patients with NB and in NB cell line culture supernatants. NB cell-derived sNKG2DL was initially cleaved by ADAM10 and ADAM17. Furthermore, sNKG2DL expression levels were positively correlated with the immunosuppressive microenvironment and poor prognosis. Tumor-derived sNKG2DL induced degradation of NKG2D

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC10236264 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature