MUC2 expression modulates immune infiltration in colorectal cancer

Area of Science:

• Oncology
• Immunology
• Gastroenterology

Background:

• Colorectal cancer (CRC) poses a significant global health burden.
• Understanding the tumor microenvironment is key for developing effective CRC therapies.
• Mucin 2 (MUC2) plays a role in gastrointestinal tract protection and has been linked to CRC progression and immune regulation.

Purpose of the Study:

• To investigate the role of MUC2 in regulating immune cell infiltration in colorectal cancer (CRC).
• To elucidate the relationship between MUC2 expression and immune cell presence within CRC models.
• To explore the impact of MUC2 knockout on T cells and NK cells in CRC spheroids.

Main Methods:

• Utilized in vitro models of CRC using HT-29 and LS-174T cell lines.
• Employed CRISPR-mediated MUC2 knockout to alter MUC2 expression.
• Analyzed immune infiltration using 3D spheroid cultures with peripheral blood mononuclear cells (PBMCs) enriched for T cells and NK cells.

Main Results:

• MUC2 knockout increased immune infiltration in HT-29 cells but not in LS-174T cells.
• LS-174T cells showed compensatory expression of MUC6 and MUC5B following MUC2 knockout, unlike HT-29 cells.
• MUC2 abundance was higher in LS-174T compared to HT-29 cells.

Conclusions:

• MUC2 functions as a physical barrier to immune cell infiltration in colorectal cancer (CRC) in vitro.
• Compensatory mucin expression (MUC6, MUC5B) in LS-174T cells maintains the barrier function after MUC2 removal.
• Targeting mucin pathways presents a potential novel therapeutic strategy for CRC.