Blockage of Core Fucosylation Reduces Cell-Surface Expression of PD-1 and Promotes Anti-tumor Immune Responses of T Cells

• DOI: 10.1016/j.celrep.2017.07.027
• Publication Date: 2017-08-01T16:15:18Z
• Authors: Masahiro Okada; Shunsuke Chikuma; Taisuke Kondo; Sana Hibino; Hiroaki Machiyama; Tadashi Yokosuka; Miyako Nakano; Akihiko Yoshimura
• Keywords: Fucosylation; Fucosyltransferase; Inducer

Programmed cell death 1 (PD-1) is highly expressed on exhausted T cells and inhibits activation. Antibodies that block the interaction between PD-1 its ligand prevent this inhibitory signal reverse dysfunction, providing beneficial anti-tumor responses in a substantial number of patients. Mechanisms for induction maintenance high expression have not been fully understood. Utilizing genome-wide loss-of-function screening method based CRISPR-Cas9 system, we identified genes involved core fucosylation pathway as positive regulators cell-surface expression. Inhibition Fut8, fucosyltransferase, by genetic ablation or pharmacologic inhibition reduced enhanced activation, leading to more efficient tumor eradication. Taken together, our findings suggest blocking can be promising strategy improving immune responses.