Zeaxanthin augments CD8⁺ effector T cell function and immunotherapy efficacy

Area of Science:

• Immunology
• Nutrition Science
• Oncology

Background:

• Mechanisms of dietary components in anti-tumor immunity are not fully understood.
• Zeaxanthin (ZEA) is a carotenoid known for eye health benefits.
• Identifying novel immunomodulators from dietary sources is crucial for cancer therapy.

Purpose of the Study:

• To identify dietary compounds that modulate anti-tumor immunity.
• To investigate the immunomodulatory effects of zeaxanthin (ZEA) on CD8+ T cells.
• To elucidate the mechanisms by which ZEA enhances anti-tumor responses.

Main Methods:

• Co-culture-based screening using a blood nutrient compound library.
• In vivo oral supplementation studies with ZEA and lutein (LUT).
• Integrated multi-omics analysis to study intracellular signaling pathways.

Main Results:

• Zeaxanthin (ZEA) enhances CD8+ T cell cytotoxicity against tumor cells.
• Oral ZEA, but not LUT, improves anti-tumor immunity in vivo.
• ZEA promotes T cell receptor (TCR) stimulation and intracellular signaling.
• ZEA augments the efficacy of anti-PD1 immune checkpoint inhibitors and TCR gene-engineered T cells.

Conclusions:

• Zeaxanthin (ZEA) possesses a previously unrecognized immunoregulatory function.
• ZEA enhances anti-tumor immunity by improving CD8+ T cell function.
• ZEA has translational potential as a dietary supplement to enhance cancer immunotherapy.