Mapping of truncated O-glycans in cancers of epithelial and non-epithelial origin
Research output: Contribution to journal › Journal article › Research › peer-review
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 language | English |
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Journal | British Journal of Cancer |
Volume | 125 |
Issue number | 9 |
Pages (from-to) | 1239-1250 |
Number of pages | 12 |
ISSN | 0007-0920 |
DOIs | |
Publication status | Published - 2021 |
- ACTIVE SPECIFIC IMMUNOTHERAPY, SIALOSYL-TN ANTIGEN, SIALYL-TN, BREAST-CANCER, CARBOHYDRATE ANTIGENS, PROTEIN GLYCOSYLATION, HUMAN-COLON, EXPRESSION, PROGNOSIS, SPECIFICITY
Research areas
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548315/pdf/41416_2021_Article_1530.pdf
Final published version
ID: 280233068