Programmed death ligand 1 gene silencing in murine glioma models reveals cell line-specific modulation of tumor growth in vivo.

ABSTRACT:

Background

Glioblastoma is the most common brain tumor in adults and virtually incurable. Therefore, new therapeutic strategies are urgently needed. Immune checkpoint inhibition has not shown activity in various phase III trials and intra- as well as intertumoral expression of programmed death ligand 1 (PD-L1) varies in glioblastoma.

Methods

We abrogated constitutive PD-L1 gene expression by CRISPR/Cas9 in murine glioma models and characterized the consequences of gene deletion in vitro and in vivo.

Results

A heterogeneous expression of Pdl1 mRNA and PD-L1 protein was detected in the glioma cell panel in vitro and in vivo. PD-L1, but not PD-L2, was inducible by interferon β and γ. Co-culture with splenocytes induced PD-L1 expression in GL-261 and SMA-560, but n

SUBMITTER: Blomberg E 

PROVIDER: S-EPMC9536295 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature