Targeting branched N-glycans and fucosylation sensitizes ovarian tumors to immune checkpoint blockade

• DOI: 10.1038/s41467-024-47069-y
• Publication Date: 2024-04-02T15:07:12Z
• Authors: Hao Nie; Pratima Saini; Taito Miyamoto; Liping Liao; Rafal J. Zielinski; Heng Liu; Wei Zhou; Chen Wang; Brennah Murphy; Martina Towers; Tyler Yang; Yuan Qi; Toshitha Kannan; Andrew Kossenkov; Hiroaki Tateno; Daniel T. Claiborne; Nan Zhang; Mohamed Abdel-Mohsen; Rugang Zhang
• Keywords: Fucosylation; Immune checkpoint

Abstract Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, it’s unclear whether homologous recombination (HR) status-dependent can be therapeutically explored. Here, we show that the inhibition of branched N -glycans sensitizes HR-proficient, but not HR-deficient, epithelial ovarian cancers (EOCs) immune checkpoint blockade (ICB). In contrast fucosylation whose EOCs anti-PD-L1 immunotherapy regardless HR-status, observe an enrichment on HR-proficient compared HR-deficient EOCs. Mechanistically, BRCA1/2 transcriptionally promotes expression MGAT5, enzyme responsible for catalyzing -glycans. The tumors augment their resistance enhancing its binding with PD-1 CD8 + T cells. orthotopic, syngeneic EOC models in female mice, inhibiting using 2-Deoxy-D-glucose EOCs, anti-PD-L1. These findings indicate as promising therapeutic targets ICB overcoming evasion.