# The Level of Antibodies to Tumor-Associated Glycans in Gastric Cancer Patients Is Lower than in Healthy Donors and Reduces with Age

## TL;DR

Gastric cancer patients have lower levels of antibodies against tumor-related sugars compared to healthy people, and these levels decrease with age.

## Contribution

The study shows reduced anti-glycan IgM levels in gastric cancer patients, suggesting a potential immunodeficiency linked to tumor development.

## Key findings

- Anti-glycan IgM levels decrease with age in both gastric cancer patients and healthy donors.
- Gastric cancer patients have significantly lower IgM levels against most glycans compared to healthy donors.
- Anti-GalNAcα antibodies bind to tumor cells and non-tumor cells in the same organ.

## Abstract

A key function of naturally occurring antibodies is to control pathologically altered cells, such as those with aberrant glycosylation. Age-related diminution in the pool of B cells producing these immunoglobulins is linked to impaired anti-tumor immunity. In this study, the levels of antibodies against tumor-associated carbohydrate antigens (TACAs)—common in gastric cancer (GC) and other malignancies—were analyzed in 235 treatment-naïve GC patients (stages I–IV) and 76 healthy donors using a printed glycan array (PGA). We found that anti-glycan IgM levels, but not IgG, reduced with age in both patients and donors. Crucially, IgM levels against most glycans were significantly lower in the GC cohort compared with healthy donors, a trend that remained after age adjustment. Furthermore, an immunohistochemical analysis revealed that human anti-GalNAcα (Tn) antibodies—a well-characterized TACA in gastrointestinal cancers—bound to tumor cells and exhibited perinuclear and membrane staining in non-tumor surface cells within the same organ. These data support the hypothesis that gastric cancer patients have reduced levels of anti-glycan IgMs, which are responsible for the early recognition of transformed cells. This specific immunodeficiency may contribute to a permissive environment for tumor development.