A study reveals that targeting branched N-glycans and fucosylation can enhance the sensitivity of HR-proficient ovarian cancers (EOCs) to immune checkpoint blockade (ICB). The research shows that inhibiting branched N-glycans in HR-proficient EOCs increases their sensitivity to anti-PD-L1 immunotherapy, while fucosylation inhibition affects EOCs regardless of HR status. Mechanistically, BRCA1/2 promote the expression of MGA15, an enzyme involved in branched N-glycan synthesis. These glycans enhance PD-L1 binding to PD-1 on CD8+ T cells, promoting immune evasion. Inhibiting branched N-glycans using 2-Deoxy-D-glucose sensitizes HR-proficient EOCs to anti-PD-L1 therapy. The study also highlights that HR-proficient EOCs exhibit higher levels of branched N-glycans compared to HR-deficient ones. These findings suggest that targeting branched N-glycans could be a promising therapeutic strategy to overcome immune evasion in HR-proficient EOCs. The study underscores the importance of glycosylation in cancer immune evasion and provides insights into the potential of targeting glycan modifications to improve immunotherapy outcomes in ovarian cancer.A study reveals that targeting branched N-glycans and fucosylation can enhance the sensitivity of HR-proficient ovarian cancers (EOCs) to immune checkpoint blockade (ICB). The research shows that inhibiting branched N-glycans in HR-proficient EOCs increases their sensitivity to anti-PD-L1 immunotherapy, while fucosylation inhibition affects EOCs regardless of HR status. Mechanistically, BRCA1/2 promote the expression of MGA15, an enzyme involved in branched N-glycan synthesis. These glycans enhance PD-L1 binding to PD-1 on CD8+ T cells, promoting immune evasion. Inhibiting branched N-glycans using 2-Deoxy-D-glucose sensitizes HR-proficient EOCs to anti-PD-L1 therapy. The study also highlights that HR-proficient EOCs exhibit higher levels of branched N-glycans compared to HR-deficient ones. These findings suggest that targeting branched N-glycans could be a promising therapeutic strategy to overcome immune evasion in HR-proficient EOCs. The study underscores the importance of glycosylation in cancer immune evasion and provides insights into the potential of targeting glycan modifications to improve immunotherapy outcomes in ovarian cancer.