Induction of PD-L1 by Nitric Oxide via JNK Activation in A172 Glioblastoma Cells

Biol Pharm Bull. 2020 Jun 1;43(6):1020-1022. doi: 10.1248/bpb.b20-00087. Epub 2020 Mar 20.

Abstract

Glioblastoma comprises 54% of all the gliomas derived from glial cells and are lethally malignant tumors of the central nervous system (CNS). Glioma cells disrupt the blood-brain barrier, leading to access of circulating immune cells to the CNS. Blocking the interaction between programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) enhances T-cell responses against tumor cells, and inhibition of the PD-1/PD-L1 pathway is used as immunotherapy for cancer, including glioblastoma. Nitric oxide (NO) has multiple physiological roles, such as immune modulation and neural transmission in the CNS. Moreover, it has both tumor-promoting and tumor-suppressive functions. We examined the effects of NOC-18, an NO donor, on the expression of PD-L1 in A172 glioblastoma cells. NOC-18 increased PD-L1 expression in A172 glioblastoma cells. Moreover, this increase is regulated via the c-Jun N-terminal kinase pathway.

Keywords: c-jun N-terminal kinase; glioblastoma; nitric oxide; programmed cell death 1 ligand 1.

MeSH terms

  • B7-H1 Antigen / genetics*
  • Cell Line, Tumor
  • Central Nervous System Neoplasms / drug therapy
  • Central Nervous System Neoplasms / genetics
  • Central Nervous System Neoplasms / metabolism
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacology*
  • Nitroso Compounds / pharmacology*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • NOC 18
  • Nitric Oxide Donors
  • Nitroso Compounds
  • Nitric Oxide
  • JNK Mitogen-Activated Protein Kinases