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

Troels Boldt Rømer1, Mikkel Koed Møller Aasted1, Sally Dabelsteen2

  • 1Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N, Denmark.

British Journal of Cancer
|September 16, 2021
PubMed
Abstract

Insights

Novel immunotherapies targeting cancer-associated truncated O-glycans, Tn and STn, show promise. This study mapped their expression in over 700 tissues, revealing specific patterns in epithelial cancers like breast, colon, and pancreas, guiding future drug development.

Area of Science:

  • Glycomics and Cancer Biology
  • Immunology and Immunotherapy
  • Translational Oncology

Background:

  • Cancer-associated truncated O-glycans, specifically Tn (GalNAcα-Ser/Thr) and STn (Neu5Acα2-6GalNacα-Ser/Thr), are emerging targets for novel immunotherapies.
  • A comprehensive, antibody-based map of these truncated O-glycans in various tumors is currently lacking, hindering effective drug development.

Purpose of the Study:

  • To create a comprehensive, antibody-based map of truncated O-glycan expression (Tn and STn) across a wide range of human healthy and tumor tissues.
  • To identify specific cancer types and subtypes where Tn and STn antigens are expressed, providing a basis for targeted immunotherapy strategies.

Main Methods:

  • Utilized monoclonal antibodies for high-throughput mapping of Tn and STn expression.
  • Analyzed over 700 tissue cores from diverse healthy and tumor tissues, including breast, colon, lung, pancreas, skin, CNS, and mesenchymal tissues.
  • Evaluated Tn expression in patient-derived xenografts to assess its stability in vivo.

Main Results:

  • High Tn-antigen expression was observed in breast (57%), colorectal (51%), and pancreatic (53%) tumors.
  • STn was predominantly found in colorectal (80%) and pancreatic (56%) tumors.
  • Truncated O-glycans were absent in mesenchymal tumors and showed low expression in CNS tumors. Tn was not detected in normal tissues, while STn was occasionally found in healthy gastrointestinal tissue. Expression decreased with tumor grade but not stage.

Conclusions:

  • Surface expression of Tn and STn is largely restricted to cancers of epithelial origin.
  • These findings highlight Tn and STn as promising and specific immunological targets for the treatment of human carcinomas.
  • The generated expression map provides crucial guidance for the development of targeted immunotherapies.

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