Microfluidic devices modulate tumor cell line susceptibility to NK cell recognition

Area of Science:

• Biotechnology
• Cell Biology
• Microfluidics

Background:

• Major histocompatibility complex class I (MHC-I) expression on cancer cells can shield them from immune detection.
• Developing targeted methods to reduce MHC-I expression is crucial for cancer immunotherapy.

Purpose of the Study:

• To develop and validate a microfluidic system for reducing MHC-I surface expression on cancer cells.
• To assess the impact of this reduction on tumor cell viability and susceptibility to natural killer (NK) cells.

Main Methods:

• A microfluidic device with antibody-functionalized surfaces (W6/32) was used to capture tumor cells.
• Cells were subjected to optimized shear stress via controlled flow rates, inducing localized stress on MHC-I molecules.
• MHC-I expression, cell viability, and NK cell cytotoxicity were analyzed using flow cytometry and confocal microscopy.

Main Results:

• A significant reduction in MHC-I surface expression was observed on treated tumor cells compared to controls.
• Healthy cells (monocytes) showed no change in MHC-I levels, indicating specificity.
• Treated tumor cells exhibited increased susceptibility to natural killer (NK) cell-mediated cytotoxicity.

Conclusions:

• Microfluidic shear stress combined with antibody binding offers a specific and effective method for reducing tumor cell MHC-I expression.
• This approach holds potential for enhancing cancer immunotherapy by making tumor cells more visible to the immune system.
• The developed system demonstrates the ability to treat eukaryotic cells without causing damage, preserving sample integrity.