Mild Reduction-Mediated NK Cell Membrane Modification for ROS Scavenging Efficacy Overcome Immunosuppressive Tumor...

Area of Science:

• Immunology
• Cancer Biology
• Biotechnology

Background:

• Solid tumors feature a tumor microenvironment (TME) with high reactive oxygen species (ROS) that impair immune cell function.
• Natural killer (NK) cells are vital for cancer immunotherapy but their efficacy is reduced by oxidative stress in the TME.
• Maintaining NK cell redox balance is critical for effective cancer immunotherapy in ROS-rich TMEs.

Purpose of the Study:

• To develop a method for reinforcing NK cell redox balance to enhance their anti-cancer activity.
• To investigate the potential of ex vivo membrane modification for improving NK cell function in oxidative stress conditions.

Main Methods:

• Engineered NK cells by introducing surface thiol groups using tris(2-carboxyethyl)phosphine (TCEP) for ROS scavenging.
• Assessed ROS scavenging capacity, intracellular ROS levels, and cytotoxicity-associated gene expression in engineered NK cells (STR-NK).
• Evaluated the cytotoxic activity of STR-NK cells against solid tumor cells in the presence of ROS.

Main Results:

• Surface-thiol-riched NK cells (STR-NK) exhibited increased membrane thiols and efficient extracellular ROS elimination.
• STR-NK cells demonstrated attenuated intracellular ROS accumulation and preserved cytotoxicity-associated gene expression under oxidative stress.
• Engineered NK cells maintained potent cytotoxicity against solid tumor cells in ROS-rich conditions.

Conclusions:

• A straightforward, scalable ex vivo membrane modification approach enhances NK cell redox balance and anti-cancer activity.
• This strategy offers a promising method to improve NK cell-based immunotherapies in ROS-enriched solid TMEs.
• Surface redox modulation of NK cells represents a viable approach to overcome oxidative stress-induced immune suppression in cancer.