TY - JOUR
T1 - Mapping of truncated O-glycans in cancers of epithelial and non-epithelial origin
AU - Rømer, Troels Boldt
AU - Aasted, Mikkel Koed Møller
AU - Dabelsteen, Sally
AU - Groen, Aaron
AU - Schnabel, Julia
AU - Tan, Edwin
AU - Pedersen, Johannes Wirenfeldt
AU - Haue, Amalie Dahl
AU - Wandall, Hans Heugh
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - ACTIVE SPECIFIC IMMUNOTHERAPY
KW - SIALOSYL-TN ANTIGEN
KW - SIALYL-TN
KW - BREAST-CANCER
KW - CARBOHYDRATE ANTIGENS
KW - PROTEIN GLYCOSYLATION
KW - HUMAN-COLON
KW - EXPRESSION
KW - PROGNOSIS
KW - SPECIFICITY
U2 - 10.1038/s41416-021-01530-7
DO - 10.1038/s41416-021-01530-7
M3 - Journal article
C2 - 34526666
VL - 125
SP - 1239
EP - 1250
JO - The British journal of cancer. Supplement
JF - The British journal of cancer. Supplement
SN - 0007-0920
IS - 9
ER -