"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," said Jing Chen, PhD, Janet Davison Rowley Distinguished Service Professor of Medicine and senior author of the study. "Our study show that a simple dietary nutrient could complement and strengthen advanced cancer treatments like immunotherapy."

How does this nutrient work?

The study builds on years of work by Chen's lab to better understand how nutrients influence the immune system. By screening a large blood nutrient library, the team identified zeaxanthin as a compound that directly enhances the activity of CD8+ T cells, a crucial type of immune cell that kills tumor cells. These cells rely on a molecular structure called the T-cell receptor (TCR) to recognize and destroy abnormal cells.

The researchers found that zeaxanthin stabilizes and strengthens the formation of TCR complex on CD8+ T cells upon interacting with the cancer cells. This, in turn, triggers more robust intracellular signaling that boosts T-cell activation, cytokine production, and tumor-killing capacity.

Zeaxanthin improves immunotherapy effects

In mouse models, dietary supplementation with zeaxanthin slowed tumor growth. Importantly, when combined with immune checkpoint inhibitors - a type of immunotherapy that has transformed cancer treatment in recent years - zeaxanthin significantly enhanced anti-tumor effects compared to immunotherapy alone.

To extend the findings, the researchers tested human T cells engineered to recognize specific tumor antigens and found that zeaxanthin treatment improved these cells' ability to kill melanoma, multiple myeloma, and glioblastoma cells in laboratory experiments.

"Our data show that zeaxanthin improves both natural and engineered T-cell responses, which suggests high translational potential for patients undergoing immunotherapies," Chen said.

A safe and accessible candidate

Zeaxanthin is sold as an over-the-counter supplement for eye health, and is naturally found in vegetables like orange peppers, spinach, and kale. It's inexpensive, widely available, well-tolerated and, most importantly, its safety profile is known - which means it can be safely tested as an adjunct to cancer therapies.

The study also reinforces the importance of a balanced diet. In their previous research, Chen's group discovered that trans-vaccenic acid (TVA), a fatty acid derived from dairy and meat, also boosts T-cell activity - but through a different mechanism. Together, the findings suggest that nutrients from both plant and animal sources may provide complementary benefits to immune health.

Clinical applications of zeaxanthin

Although the results are promising, the researchers emphasize that the work is still at an early stage. Most of the findings come from laboratory experiments and animal studies. Thus, clinical trials will be needed to determine whether zeaxanthin supplements can improve outcomes for cancer patients.

"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 study, "Zeaxanthin augments CD8+ effector T cell function and immunotherapy efficacy," was supported by grants from the National Institutes of Health, the Ludwig Center at the University of Chicago, and the Harborview Foundation Gift Fund.

Additional authors include Freya Zhang, Jiacheng Li, Rukang Zhang, Jiayi Tu, Zhicheng Xie, Takemasa Tsuji, Hardik Shah, Matthew Ross, Ruitu Lyu, Junko Matsuzaki, Anna Tabor, Kelly Xue, Chunzhao Yin, Hamed R. Youshanlouei, Syed Shah, Michael W. Drazer, Yu-Ying He, Marc Bissonnette, Jun Huang, Chuan He, Kunle Odunsi, and Hao Fan from the University of Chicago; Fatima Choudhry from DePaul University, Chicago; Yuancheng Li and Hui Mao from Emory University School of Medicine, Atlanta; Lei Dong from University of Texas Southwestern Medical Center, Dallas; and Rui Su from Beckman Research Institute, City of Hope, Duarte, CA.