Dataset Information

Targeting Truncated O-Glycan Elicits Dual T Cell Immunity and Overcomes MHC-I Heterogeneity to Design Effective Cancer Vaccine

ABSTRACT: Aberrant O-glycosylation is a hallmark of cancer, but its contribution to immune evasion is unclear. Using CRISPR–Cas9 to delete GalNAc-transferases, particularly Galnt7, in tumor cells, we reduced mucin-type O-glycan truncation. This remodeling activated dendritic cell– and T cell–dependent immunity, eradicating established tumors, preventing metastasis, and generating durable memory. It enhanced clearance of MHC class I–positive tumors via coordinated CD8⁺ and CD4⁺ T cell responses, and uniquely enabled CD4⁺ T cell–mediated elimination of MHC class I–deficient tumors, which evade cytotoxic T lymphocyte surveillance. Tumor cells with reduced O-glycan truncation served as potent whole-cell vaccines, with efficacy further improved by radiotherapy. These findings establish glycosylation as a central regulator of tumor immune evasion and define a broadly applicable vaccine platform that bypasses the limitations of neoantigen-based approaches for low-immunogenicity cancers.

ORGANISM(S): Mus musculus

PROVIDER: GSE309508 | GEO | 2025/10/02

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Various cancers such as colorectal cancer (CRC) are associated with alterations in protein glycosylation. CRC cell lines are frequently used to study these (glyco)biological changes and their mechanisms. However, differences between CRC cell lines with regard to their glycosylation have hitherto been largely neglected. Here, we comprehensively characterized the N-glycan profiles of 25 different CRC cell lines, derived from primary tumors and metastatic sites, in order to investigate their potential as glycobiological tumor model systems and to reveal glycans associated with cell line phenotypes. We applied an optimized, high-throughput membrane-based enzymatic glycan release for small sample amounts. Released glycans were derivatized to stabilize and differentiate between a2,3- and a2,6-linked N-acetylneuraminic acids, followed by N-glycosylation analysis by MALDI-TOF(/TOF)-MS. Our results showed pronounced differences between the N-glycosylation patterns of CRC cell lines. CRC cell line profiles differed from tissue-derived N-glycan profiles with regard to their high-mannose N-glycan content but showed a large overlap for complex type N-glycans, supporting their use as a glycobiological cancer model system. Importantly, we could show that the high-mannose N-glycans did not only occur as intracellular precursors but were also present at the cell surface. The obtained CRC cell line N-glycan features were not clearly correlated with mRNA expression levels of glycosyltransferases, demonstrating the usefulness of performing the structural analysis of glycans. Finally, correlation of CRC cell line glycosylation features with cancer cell markers and phenotypes revealed an association between highly fucosylated glycans and CDX1 and/or villin mRNA expression that both correlate with cell differentiation. Together, our findings provide new insights into CRC-associated glycan changes and setting the basis for more in-depth experiments on glycan function and regulation.

Project description:This data set was downloaded from MetaboLights (http://www.ebi.ac.uk/metabolights/) accession number MTBLS227 Abstract:"Various cancers such as colorectal cancer (CRC) are associated with alterations in protein glycosylation. CRC cell lines are frequently used to study these (glyco)biological changes and their mechanisms. However, differences between CRC cell lines with regard to their glycosylation have hitherto been largely neglected. Here, we comprehensively characterized the N-glycan profiles of 25 different CRC cell lines, derived from primary tumors and metastatic sites, in order to investigate their potential as glycobiological tumor model systems and to reveal glycans associated with cell line phenotypes. We applied an optimized, high-throughput membrane-based enzymatic glycan release for small sample amounts. Released glycans were derivatized to stabilize and differentiate between a2,3- and a2,6-linked N-acetylneuraminic acids, followed by N-glycosylation analysis by MALDI-TOF(/TOF)-MS. Our results showed pronounced differences between the N-glycosylation patterns of CRC cell lines. CRC cell line profiles differed from tissue-derived N-glycan profiles with regard to their high-mannose N-glycan content but showed a large overlap for complex type N-glycans, supporting their use as a glycobiological cancer model system. Importantly, we could show that the high-mannose N-glycans did not only occur as intracellular precursors but were also present at the cell surface. The obtained CRC cell line N-glycan features were not clearly correlated with mRNA expression levels of glycosyltransferases, demonstrating the usefulness of performing the structural analysis of glycans. Finally, correlation of CRC cell line glycosylation features with cancer cell markers and phenotypes revealed an association between highly fucosylated glycans and CDX1 and/or villin mRNA expression that both correlate with cell differentiation. Together, our findings provide new insights into CRC-associated glycan changes and setting the basis for more in-depth experiments on glycan function and regulation."

Dataset Information

Targeting Truncated O-Glycan Elicits Dual T Cell Immunity and Overcomes MHC-I Heterogeneity to Design Effective Cancer Vaccine

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets