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

Troels Boldt Rømer, Mikkel Koed Møller Aasted, Sally Dabelsteen, Aaron Groen, Julia Schnabel, Edwin Tan, Johannes Wirenfeldt Pedersen, Amalie Dahl Haue, Hans Heugh Wandall*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

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.

OriginalsprogEngelsk
TidsskriftBritish Journal of Cancer
Vol/bind125
Udgave nummer9
Sider (fra-til)1239-1250
Antal sider12
ISSN0007-0920
DOI
StatusUdgivet - 2021

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