Immunomodulatory effects of galectins 1 and 3 in an in vitro co-culture of colorectal adenocarcinoma cells and peripheral blood mononuclear cells

Background. Tumor immune evasion plays a key role in the progression of colorectal cancer (CRC). β-galactoside-binding proteins galectin-1 and galectin-3 may be important mediators of this process; however, their specific immunomodulatory effects in CRC require further investigation.

Objective. To study the in vitro effects of galectin-1 and galectin-3, expressed by colon adenocarcinoma cells, on the secretion of IFNγ, IL-17A, and TGFβ1 by peripheral blood mononuclear cells (PBMCs) from CRC patients and healthy donors.

Design and method. The human colorectal adenocarcinoma cell line COLO 201 was co-cultured with PBMCs from CRC patients and healthy donors in the presence or absence of selective galectin-1 (OTX 008) and galectin-3 (GB1107) inhibitors. The concentrations of IFNγ, IL-17A, and TGFβ1 in the culture supernatants were measured by enzyme-linked immunosorbent assay.

Results. Inhibition of galectin-1 in COLO 201-PBMC co-cultures significantly increased IFNγ and IL-17A production and decreased TGFβ1 secretion by PBMCs from both CRC patients and healthy donors. In co-cultures with patient-derived PBMCs, galectin-3 inhibition had a similar effect. However, in co-cultures with healthy donor cells, it was accompanied by suppressed IL-17A production and an increased TGFβ1 level. Combined galectin-1,3 blockade in co-cultures containing PBMCs from CRC patients caused a more pronounced reduction in TGFβ1 levels than individual inhibition; at the same time, changes in IFNγ and IL-17A levels mirrored the effects of single inhibitors.

Conclusion. Colorectal cancer cell-derived galectin-1 and galectin-3 mediate in vitro disruption of the cytokine profile in peripheral blood mononuclear cells. Galectin-1 exhibits tolerogenic properties, while the effect of galectin-3 depends on the source of the target immune cells (PBMCs from CRC patients or healthy donors).

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