"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.

In a study published in Nature Communications, the researchers demonstrate how the tool, called DOLPHIN, could one day be used by doctors to catch diseases earlier and guide treatment options.

"This tool has the potential to help doctors match patients with the therapies most likely to work for them, reducing trial-and-error in treatment," said senior author Jun Ding, assistant professor in McGill's Department of Medicine and a junior scientist at the Research Institute of the McGill University Health Centre.

Zooming in on genetic building blocks

Disease markers are often subtle changes in RNA expression that can indicate when a disease is present, how severe it may become or how it might respond to treatment.

Conventional gene-level methods of analysis collapse these markers into a single count per gene, masking critical variation and capturing only the tip of the iceberg, said the researchers.

Now, advances in artificial intelligence have made it possible to capture the fine-grained complexity of single-cell data. DOLPHIN moves beyond gene-level, zooming in to see how genes are spliced together from smaller pieces called exons to provide a clearer view of cell states.

"Genes are not just one block, they're like Lego sets made of many smaller pieces," said first author Kailu Song, a PhD student in McGill's Quantitative Life Sciences program. "By looking at how those pieces are connected, our tool reveals important disease markers that have long been overlooked."

In one test case, DOLPHIN analyzed single-cell data from pancreatic cancer patients and found more than 800 disease markers missed by conventional tools. It was able to distinguish patients with high-risk, aggressive cancers from those with less severe cases, information that would help doctors choose the right treatment path.

A step toward 'virtual cells'

More broadly, the breakthrough lays the foundation for achieving the long-term goal of building digital models of human cells. DOLPHIN generates richer single-cell profiles than conventional methods, enabling virtual simulations of how cells behave and respond to drugs before moving to lab or clinical trials, saving time and money.

The researchers' next step will be to expand the tool's reach from a few datasets to millions of cells, paving the way for more accurate virtual cell models in the future.

About the study

"DOLPHIN advances single-cell transcriptomics beyond gene level by leveraging exon and junction reads" by Kailu Song and Jun Ding et al., was published inNature Communications.

This research was supported the Meakins-Christie Chair in Respiratory Research, the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada and the Fonds de recherche du Québec.

A new study may pave the way for a new generation of cancer therapies -- by training the body's own immune system to work smarter and hit harder. Led by PhD student Omri Yosef and Prof. Michael Berger from the Faculty of Medicine at Hebrew University, in collaboration with Prof. Magdalena Huber of Philipps University of Marburg and Prof. Eyal Gottlieb of the University of Texas MD Anderson Cancer Center, the international team discovered that fine-tuning immune cells metabolism dramatically improves their ability to destroy cancer.

At the heart of the research is a powerful insight: when T cells -- key players in the immune system -- are forced to rewire how they convert energy, they become significantly more effective at identifying and attacking tumors.

"By disabling Ant2, we triggered a complete shift in how T cells produce and use energy," explains Prof. Berger. "This reprogramming made them significantly better at recognizing and killing cancer cells." In simpler terms, blocking this protein forces the immune cells to adapt their metabolism, turning them into stronger, faster, and more aggressive cancer fighters.

Published in Nature Communications, the study focuses on the mitochondria -- the "metabolic hub" of cells. By deliberately disrupting a specific energy pathway inside T cells, the team essentially rewired the cells' engines, creating a state of heightened readiness and potency. The altered T cells exhibited greater stamina, faster replication, and sharper targeting of cancerous threats.

Perhaps most importantly, the researchers showed that this metabolic rewiring can be triggered not only through genetic modifications but also with drugs -- opening the door for potential clinical applications.

This discovery is part of a growing movement in cancer immunotherapy that focuses not only on guiding the immune system but upgrading its inner machinery. While more studies and clinical trials are needed, the implications of this breakthrough are promising: new treatments that harness the body's own defenses, fine-tuned for peak performance.

"This work highlights how deeply interconnected metabolism and immunity truly are," says Prof. Berger. "By learning how to control the power source of our immune cells, we may be able to unlock therapies that are both more natural and more effective."