MHC class I polypeptide-related sequence B shedding modulates pancreatic tumor immunity via the activation of NKG2D^Low T cells.

ABSTRACT: Natural killer group 2 member D ligands (NKG2DLs) are expressed as stress response proteins in cancer cells. NKG2DLs induce immune cell activation or tumor escape responses, depending on their expression. Human pancreatic cancer cells, PANC-1, express membrane MHC class I polypeptide-related sequence A/B (mMICA/B), whereas soluble MICB (sMICB) is detected in the culture supernatant. We hypothesized that sMICB saturates NKG2D in NKG2D^Low T cells and inhibits the activation signal from mMICB to NKG2D. Knockdown of MICB by siRNA reduced sMICB level, downregulated mMICB expression, maintained NKG2D^Low T cell activation, and inhibited NKG2D^High T cell activation. To maintain mMICB expression and downregulate sMICB expression, we inhibited a disintegrin and metal

SUBMITTER: Toyoda H 

PROVIDER: S-EPMC11461622 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature