Abstract
Over the past decades, a large amount of data has been accumulated in various subfields of glycobiology. However, much clinically relevant data and many tools are still not widely used in medicine. Synthetic glycoconjugates with the known structure of glycans are an accurate tool for the study of glycan-binding proteins. We used polyacrylamide glycoconjugates (PGs) including PGs with tumour-associated glycans (TAGs) in immunoassays to assess the prognostic potential of the serum level of anti-glycan antibodies (AG Abs) in gastrointestinal cancer patients and found an association of AG Abs with survival. The specificity of affinity-isolated AG Abs was investigated using synthetic and natural glycoconjugates. AG Abs showed mainly a low specificity to tumour-associated and tumour-derived mucins; therefore, the protective role of the examined circulating AG Abs against cancer remains a challenge. In this review, our findings are analysed and discussed in the context of the contribution of bacteria to the AG Abs stimulus and cancer progression. Examples of the influence of pathogenic bacteria colonising tumours on cancer progression and patient survival through mechanisms of interaction with tumours and dysregulated immune response are considered. The possibilities and problems of the integrative study of AG Abs and the microbiome using high-performance technologies are discussed.
Highlights
We studied the specificity of anti-glycan antibodies (AG Abs) isolated from the serum of long-term survivors
We studied the level of IgG Abs that are reactive to tumour-associated glycans (TAGs), namely anti-TFα, -Tn, and cancer-irrelevant xenoreactive anti-αGal, as well as anti-GalNAcβ and -PFdi, in the sera of patients with gastric, colorectal, and breast cancer [8,19,20,21,22]
Anti-TF IgG Abs showed high reactivity to mucins isolated from breast cancer tissue but for rare specimens, which presumably was due to the admixture of bacterial glycoconjugates, since a diverse microbiota can colonise malignant breast tumours [49]
Summary
Simple and complex carbohydrates (glycans, glycoconjugates) play a vital role in organisms. Changes in the glycosylation pattern make the tumour cells evade immunosurveillance [2]. In this respect, the role of anti-glycan antibodies (AG Abs) in the mechanisms of anticancer defence remains unclear. The circulating auto-Abs to TAGs might protect against cancer; their protective role and association with cancer progression remain poorly understood. This paper analyses the research results and discusses the possibilities and challenges of an integrative approach to the study of AG Abs and pathogenic bacteria colonising tumours and their involvement in the progression of cancer and dysregulation of the immune response in the tumour microenvironment
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