Zeaxanthin augments CD8+ effector T cell function and immunotherapy efficacy
The detailed mechanisms underlying the regulatory significance of dietary components in modulating anti-tumor immunity remain largely unknown. Here, we apply a co-culture-based screening approach using a blood nutrient compound library and identify zeaxanthin (ZEA), a dietary carotenoid pigment found in many fruits and vegetables and known for its role in eye health, as an immunomodulator that enhances the cytotoxicity of CD8<sup>+</sup> T cells against tumor cells. Oral supplementation with ZEA, but not its structural isomer lutein (LUT), enhances anti-tumor immunity in vivo. Integrated multi-omics mechanistic studies reveal that ZEA promotes T cell receptor (TCR) stimulation on the CD8<sup>+</sup> T cell surface, leading to improved intracellular TCR signaling for effector T cell function. Hence, ZEA treatment augments the efficacy of anti-PD1 immune checkpoint inhibitor in vivo and the cytotoxicity of human TCR gene-engineered CD8<sup>+</sup> T cells in vitro. Our findings uncover a previously unknown immunoregulatory function of ZEA, which has translational potential as a dietary element in bolstering immunotherapy.
Authors
- Ruitu Lyu (ORCID: https://orcid.org/0000-0003-4597-1604)
- Junko Matsuzaki (ORCID: https://orcid.org/0000-0002-2555-1234)
- Kunle Odunsi (ORCID: https://orcid.org/0000-0002-4444-7651)
- Yu‐Ying He (ORCID: https://orcid.org/0000-0002-2665-7962)
- Michael W. Drazer (ORCID: https://orcid.org/0000-0002-8171-4106)
- Kai Xue (ORCID: https://orcid.org/0000-0003-3131-0063)
- Hamed Rahmani Youshanlouei (ORCID: https://orcid.org/0000-0003-0263-8895)
- Ala E. Tabor (ORCID: https://orcid.org/0000-0001-7147-1078)
- Zhicheng Xie (ORCID: https://orcid.org/0009-0003-3990-0508)
- Matthew O. Ross (ORCID: https://orcid.org/0000-0003-2115-9806)
- B M Bissonnette
- Freya Q. Zhang (ORCID: https://orcid.org/0000-0002-2596-0433)
- Hao Fan (ORCID: https://orcid.org/0000-0001-5245-9698)
- Hardik Shah (ORCID: https://orcid.org/0000-0001-8408-5686)
- Jiayi Tu
- Hui Mao (ORCID: https://orcid.org/0000-0002-0147-6022)
- Jiacheng Li (ORCID: https://orcid.org/0000-0003-4884-9786)
- Lei Dong (ORCID: https://orcid.org/0000-0001-9574-0148)
- Jun Huang (ORCID: https://orcid.org/0000-0002-1318-8562)
- Rukang Zhang (ORCID: https://orcid.org/0000-0001-9554-4999)
- Chuan He (ORCID: https://orcid.org/0000-0003-4319-7424)
- Jing Chen (ORCID: https://orcid.org/0000-0002-5376-9062)
- Rui Su (ORCID: https://orcid.org/0000-0002-4807-6229)
- Yuancheng Li (ORCID: https://orcid.org/0000-0003-1994-6093)
- Chunzhao Yin
- Syed Shah (ORCID: https://orcid.org/0000-0003-4992-934X)
- Takemasa Tsuji
- Fatima Choudhry
Institutions
- DePaul University (US)
- Emory University (US)
- University of Chicago (US)
- City of Hope (US)
- Beckman Research Institute
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102324
- Citations
- 2
- Primary Topic
- Transgenic Plants and Applications
- Type
- article
- Field-Weighted Citation Impact
- 2.47
Funders
- National Institutes of Health