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- Title
Mapping of truncated O-glycans in cancers of epithelial and non-epithelial origin.
- Authors
Rømer, Troels Boldt; Aasted, Mikkel Koed Møller; Dabelsteen, Sally; Groen, Aaron; Schnabel, Julia; Tan, Edwin; Pedersen, Johannes Wirenfeldt; Haue, Amalie Dahl; Wandall, Hans Heugh
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
British Journal of Cancer, 2021, Vol 125, Issue 9, p1239
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-021-01530-7