University of Chicago scientists have identified zeaxanthin, a plant-derived carotenoid commonly used in eye health supplements, as a potent enhancer of cancer immunotherapy effectiveness. The groundbreaking research, published in Cell Reports Medicine, reveals that this naturally occurring nutrient can significantly boost the cancer-fighting abilities of CD8+ T lymphocytes, opening new avenues for improving current cancer treatments.
Novel Mechanism of Immune Enhancement
The research team, led by Jing Chen, PhD, Janet Davison Rowley Distinguished Service Professor of Medicine, discovered zeaxanthin's immune-boosting properties through systematic screening of a large blood nutrient library. The study demonstrates that zeaxanthin directly enhances CD8+ T cell activity by stabilizing and strengthening the formation of T-cell receptor (TCR) complexes when these immune cells interact with cancer cells.
"We were surprised to find that zeaxanthin, already known for its role in eye health, has a completely new function in boosting anti-tumor immunity," Chen explained. "Our study shows that a simple dietary nutrient could complement and strengthen advanced cancer treatments like immunotherapy."
The molecular mechanism involves zeaxanthin's ability to reinforce TCR complex assembly, which amplifies intracellular signaling pathways critical for T-cell activation. This enhancement leads to increased production of cytokines and other effector molecules that empower CD8+ T cells to mount more robust responses against cancerous cells.
Synergistic Effects with Current Therapies
In mouse cancer models, dietary zeaxanthin supplementation markedly slowed tumor progression. More significantly, when combined with immune checkpoint inhibitors—a revolutionary class of immunotherapies—zeaxanthin produced synergistic anti-tumor effects that exceeded what immunotherapy alone could achieve.
The researchers extended their investigations to human cells, engineering CD8+ T cells to express receptors targeting specific tumor antigens. Upon zeaxanthin administration, these modified T cells exhibited enhanced cytotoxicity against diverse cancer cell lines, including melanoma, multiple myeloma, and glioblastoma.
"Our data show that zeaxanthin improves both natural and engineered T-cell responses, which suggests high translational potential for patients undergoing immunotherapies," Chen noted.
Clinical Accessibility and Safety Profile
Zeaxanthin's therapeutic potential is enhanced by its established safety profile and widespread availability. The nutrient is commonly sold as an over-the-counter supplement for eye health and is naturally abundant in vegetables such as spinach, kale, and orange bell peppers. Its known safety profile reduces barriers to clinical testing as an adjuvant therapy.
The study reinforces broader concepts in nutritional immunology, building on the research team's previous discovery of trans-vaccenic acid (TVA), a fatty acid from dairy and meat products that also stimulates T-cell activity through different molecular pathways. Together, these findings suggest that nutrients from both plant and animal sources may provide complementary benefits to immune health.
Future Clinical Development
Despite the compelling preclinical results, the researchers emphasize that clinical trials are essential to determine whether zeaxanthin supplementation can meaningfully improve patient responses to immunotherapies and impact long-term survival. Such trials will help establish optimal dosing, timing, and formulation strategies to maximize therapeutic benefit.
"Our findings open a new field of nutritional immunology that looks at how specific dietary components interact with the immune system at the molecular level," Chen said. "With more research, we may discover natural compounds that make today's cancer therapies more effective and accessible."
The research was supported by grants from the National Institutes of Health, the Ludwig Center at the University of Chicago, and the Harborview Foundation Gift Fund, with collaborative contributions from researchers at DePaul University, Emory University School of Medicine, University of Texas Southwestern Medical Center, and Beckman Research Institute.
