Targeting cancer glycosylation repolarizes tumor-associated macrophages allowing effective immune checkpoint blockade.

ABSTRACT: Immune checkpoint blockade (ICB) has substantially improved the prognosis of patients with cancer, but the majority experiences limited benefit, supporting the need for new therapeutic approaches. Up-regulation of sialic acid-containing glycans, termed hypersialylation, is a common feature of cancer-associated glycosylation, driving disease progression and immune escape through the engagement of Siglec receptors on tumor-infiltrating immune cells. Here, we show that tumor sialylation correlates with distinct immune states and reduced survival in human cancers. The targeted removal of Siglec ligands in the tumor microenvironment, using an antibody-sialidase conjugate, enhanced antitumor immunity and halted tumor progression in several murine models. Using single-cell RNA sequencing, we reve

SUBMITTER: Stanczak MA 

PROVIDER: S-EPMC9812757 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature