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Review
. 2020 Feb:47:101389.
doi: 10.1016/j.smim.2020.101389. Epub 2020 Jan 9.

Tumor-associated O-glycans of MUC1: Carriers of the glyco-code and targets for cancer vaccine design

Donella M Beckwith  1 , Maré Cudic  2
Affiliations
Review

Tumor-associated O-glycans of MUC1: Carriers of the glyco-code and targets for cancer vaccine design

Donella M Beckwith et al. Semin Immunol. 2020 Feb.

Abstract

The transformation from normal to malignant phenotype in human cancers is associated with aberrant cell-surface glycosylation. It has frequently been reported that MUC1, the heavily glycosylated cell-surface mucin, is altered in both, expression and glycosylation pattern, in human carcinomas of the epithelium. The presence of incomplete or truncated glycan structures, often capped by sialic acid, commonly known as tumor-associated carbohydrate antigens (TACAs), play a key role in tumor initiation, progression, and metastasis. Accumulating evidence suggests that expression of TACAs is associated with tumor escape from immune defenses. In this report, we will give an overview of the oncogenic functions of MUC1 that are exerted through TACA interactions with endogenous carbohydrate-binding proteins (lectins). These interactions often lead to creation of a pro-tumor microenvironment, favoring tumor progression and metastasis, and tumor evasion. In addition, we will describe current efforts in the design of cancer vaccines with special emphasis on synthetic MUC1 glycopeptide vaccines. Analysis of the key factors that govern structure-based design of immunogenic MUC1 glycopeptide epitopes are described. The role of TACA type, position, and density on observed humoral and cellular immune responses is evaluated.

Keywords: Immune response; Lectins; MUC1; Tumor-associated carbohydrate antigens; Vaccines.

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Conflict of interest statement

Declaration of Competing Interest The authors declare no competing financial interests.

Figures

Fig. 1.
Fig. 1.
Structural differences between normal and tumor-associated MUC1.
Fig 2.
Fig 2.
Core O-glycan and TACA structures.
Fig. 3.
Fig. 3.
Ligands for TA MUC1 and the TACAs that ligate them.
Fig. 4.
Fig. 4.
Galectin-3 interaction with TF antigen of TA MUC1 promote heterotypic cancer-endothelial adhesion and cancer cell homotypic aggregation. Integrins and VCAM-1 are additional mediators in the adhesion process.
Fig. 5.
Fig. 5.
Cancer vaccines either aim to prevent precancerous tumors from shifting into a microenvironment that favors regulatory and immunosuppressive mechanisms (preventive) or to restore immunosurveillance (therapeutic).
Fig. 6.
Fig. 6.
Vaccine formulations represented in this review.
See this image and copyright information in PMC

References

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