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

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Background Novel immunotherapies targeting cancer-associated truncated O-glycans Tn (GalNAc alpha-Ser/Thr) and STn (Neu5Ac alpha 2-6GalNac alpha-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.

Original languageEnglish
JournalBritish Journal of Cancer
Volume125
Issue number9
Pages (from-to)1239-1250
Number of pages12
ISSN0007-0920
DOIs
Publication statusPublished - 2021

    Research areas

  • ACTIVE SPECIFIC IMMUNOTHERAPY, SIALOSYL-TN ANTIGEN, SIALYL-TN, BREAST-CANCER, CARBOHYDRATE ANTIGENS, PROTEIN GLYCOSYLATION, HUMAN-COLON, EXPRESSION, PROGNOSIS, SPECIFICITY

ID: 280233068