N-glycosylation of PD-L1 modulates the efficacy of immune checkpoint blockades targeting PD-L1 and PD-1.

ABSTRACT:

Background

The PD-L1/PD-1 pathway is crucial for immune regulation and has become a target in cancer immunotherapy. However, in order to improve patient selection for immune checkpoint blockade (ICB) therapies, better selection criteria are needed. This study explores how the N-glycosylation of PD-L1 affects its interaction with PD-1 and ICB efficacy, focusing on its four N-linked glycosylation sites: N35, N192, N200, and N219.

Methods

Human PD-L1 glycosylation mutants-at each individual site or at all four sites together (Nx4)-were tested for their functional interaction with PD-1 using an artificial immune checkpoint reporter assay (IcAR-PD1). The blocking efficacy of anti-PD-L1 and anti-PD-1 antibodies was evaluated using human breast cancer cell lines (MDA-MB231 and MCF7

SUBMITTER: Kaufman B 

PROVIDER: S-EPMC12065222 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature