Mapping of truncated O-glycans in cancers of epithelial and non-epithelial origin.

Abstract

BACKGROUND:

Novel immunotherapies targeting cancer-associated truncated O-glycans Tn (GalNAcα-Ser/Thr) and STn (Neu5Acα2-6GalNacα-Ser/Thr) are promising strategies for cancer treatment. However, no comprehensive, antibody-based mapping of truncated O-glycans in tumours exist to guide drug development.

METHODS:

We used monoclonal antibodies to map the expression of truncated O-glycans in >700 tissue cores representing healthy and tumour tissues originating from breast, colon, lung, pancreas, skin, CNS and mesenchymal tissue. Patient-derived xenografts were used to evaluate Tn expression upon tumour engraftment.

RESULTS:

The Tn-antigen was highly expressed in breast (57%, n = 64), colorectal (51%, n = 140) and pancreatic (53%, n = 108) tumours, while STn was mainly observed in colorectal (80%, n = 140) and pancreatic (56%, n = 108) tumours. We observed no truncated O-glycans in mesenchymal tumours (n = 32) and low expression of Tn (5%, n = 87) and STn (1%, n = 75) in CNS tumours. No Tn-antigen was found in normal tissue (n = 124) while STn was occasionally observed in healthy gastrointestinal tissue. Surface expression of Tn-antigen was identified across several cancers. Tn and STn expression decreased with tumour grade, but not with cancer stage. Numerous xenografts maintained Tn expression.

CONCLUSIONS:

Surface expression of truncated O-glycans is limited to cancers of epithelial origin, making Tn and STn attractive immunological targets in the treatment of human carcinomas.

• Authors: Troels Boldt Rømer, Mikkel Koed Møller Aasted, Sally Dabelsteen, Aaron Groen, Julia Schnabel, Edwin Tan, Johannes Wirenfeldt Pedersen, Amalie Dahl Haue, Hans Heugh Wandall
• Journal: British journal of cancer (Br J Cancer) Vol. 125 Issue 9 Pg. 1239-1250 (10 2021) ISSN: 1532-1827 [Electronic] England
• PMID: 34526666 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Antibodies, Monoclonal
• Antigens, Tumor-Associated, Carbohydrate
• Tn antigen

Topics

• Animals
• Antibodies, Monoclonal (immunology)
• Antigens, Tumor-Associated, Carbohydrate (metabolism)
• Case-Control Studies
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Humans
• Mice
• Neoplasm Grading
• Neoplasm Staging
• Neoplasm Transplantation
• Neoplasms (classification, metabolism, pathology)
• Tissue Array Analysis (methods)
• Up-Regulation