Colon Adenocarcinoma Cell-Derived Galectins-1,3 Modulate Differentiation of CD4⁺ T Lymphocytes In Vitro

Area of Science:

• Immunology
• Cancer Biology
• Molecular Biology

Background:

• Galectins, particularly galectin-1 and galectin-3, are implicated in cancer progression and immune modulation.
• Colorectal adenocarcinoma cells express galectins that can influence the tumor microenvironment.
• CD4+ T lymphocyte differentiation is crucial for adaptive immunity and is often dysregulated in cancer.

Purpose of the Study:

• To investigate the effect of selective galectin-1 and galectin-3 inhibition on CD4+ T lymphocyte differentiation.
• To analyze the impact of these inhibitors on key transcription factors (T-bet, RORC2, Foxp3) in T cells from colorectal cancer patients and healthy donors.

Main Methods:

• Co-culture of COLO 201 colorectal adenocarcinoma cells with peripheral blood mononuclear cells (PBMCs) from colorectal cancer patients and healthy donors.
• Treatment with galectin-1 inhibitor (OTX 008), galectin-3 inhibitor (GB1107), or both inhibitors.
• Analysis of mRNA expression levels of T-bet (TBX21), RORC2, and Foxp3 transcription factors in PBMCs using quantitative PCR.

Main Results:

• Inhibition of galectin-1 increased TBX21 and RORC2 mRNA expression while decreasing FOXP3 mRNA expression in PBMCs from both patient and healthy donor groups.
• Galectin-3 inhibition in patient-derived PBMCs showed similar effects to galectin-1 inhibition.
• In healthy donor PBMCs, galectin-3 blockade suppressed RORC2 and induced FOXP3 expression.
• Simultaneous inhibition of both galectin-1 and galectin-3 resulted in the most significant downregulation of FOXP3 expression.

Conclusions:

• Selective inhibition of galectin-1 and galectin-3 differentially modulates CD4+ T lymphocyte differentiation.
• The combined inhibition of galectin-1 and galectin-3 holds potential for reprogramming T cell responses in the context of colorectal cancer.
• Targeting galectins may offer a therapeutic strategy to influence the immune microenvironment in colorectal adenocarcinoma.