Zeaxanthin boosts immune cell function to enhance cancer immunotherapy
Research reveals that zeaxanthin, a carotenoid found in corn, leafy greens, and egg yolks, significantly enhances CD8+ T cell cytotoxicity against tumours. The compound promotes T cell receptor stimulation and improves responses to immune checkpoint inhibitors, suggesting new dietary approaches to cancer treatment.
Scientists have discovered that zeaxanthin, a naturally occurring carotenoid pigment abundant in corn, spinach, and other colourful foods, can substantially enhance the cancer-fighting capabilities of immune cells. The research, published in Cell Reports Medicine on 16 September 2025, demonstrates for the first time that this common dietary compound directly strengthens CD8+ T cell responses against tumours.
Plant pigment emerges as immune system enhancer
The University of Chicago-led research team identified zeaxanthin through a systematic screening of blood nutrients, testing their effects on immune cell function. Unlike its structural cousin lutein, zeaxanthin specifically enhanced the cytotoxic activity of CD8+ T cells – the immune system’s primary tumour-killing cells.
“The detailed mechanisms underlying the regulatory significance of dietary components in modulating anti-tumour immunity remain largely unknown,” the authors noted in their findings. Their discovery fills a critical gap in understanding how specific nutrients influence immune responses.
In laboratory studies, mice receiving oral zeaxanthin supplementation showed significantly reduced tumour growth in melanoma and colon cancer models. The effect was completely dependent on CD8+ T cells, as depleting these immune cells eliminated zeaxanthin’s anti-tumour benefits.
Mechanism reveals cellular communication enhancement
The research team uncovered that zeaxanthin works by promoting T cell receptor (TCR) complex formation on the surface of CD8+ T cells. Using advanced imaging techniques and biochemical assays, they demonstrated that zeaxanthin directly binds to TCR components and stabilises their assembly, leading to enhanced intracellular signalling.
“ZEA promotes T cell receptor (TCR) stimulation on the CD8+ T cell surface, leading to improved intracellular TCR signalling for effector T cell function,” the researchers explained in their analysis.
This enhanced signalling activates multiple downstream pathways, including calcium signalling and nuclear factor κB activation, which are crucial for T cell function. The specificity was remarkable – while zeaxanthin powerfully activated these pathways, lutein showed minimal effects despite their nearly identical chemical structures.
Immunotherapy combination shows promise
The practical implications became clear when researchers tested zeaxanthin alongside anti-PD-1 immunotherapy, a widely used cancer treatment. The combination produced synergistic effects, with zeaxanthin-supplemented mice showing superior tumour control compared to either treatment alone.
Flow cytometry analysis revealed that oral zeaxanthin supplementation significantly increased both the number and activation status of tumour-infiltrating CD8+ T cells. These immune cells showed elevated expression of activation markers and increased production of anti-tumour cytokines including interferon-γ and tumour necrosis factor-α.
Human cell studies confirm translational potential
The research extended beyond animal models to human immune cells. Zeaxanthin treatment enhanced the function of human CD8+ T cells from healthy donors, increasing their production of key cytokines. More significantly, the compound improved the cancer-killing ability of engineered TCR-T cells, a cutting-edge cellular therapy approach.
“ZEA treatment augments the efficacy of anti-PD1 immune checkpoint inhibitor in vivo and the cytotoxicity of human TCR gene-engineered CD8+ T cells in vitro,” the authors reported, highlighting the therapeutic potential across multiple treatment modalities.
The effect proved highly selective – zeaxanthin enhanced CD8+ T cell function without significantly affecting other immune cell populations, including CD4+ T cells, B cells, or macrophages within the tumour microenvironment.
Structural specificity determines biological activity
To understand why zeaxanthin succeeded where similar compounds failed, researchers tested six structurally related carotenoids. Only zeaxanthin and fucoxanthin (found in marine algae) showed significant activity, despite all compounds sharing conjugated double-bond structures traditionally associated with antioxidant properties.
The findings revealed that antioxidant activity alone was insufficient. Instead, zeaxanthin’s unique symmetrical structure with specific ring arrangements at both ends of its conjugated chain proved essential for biological activity.
Dietary implications and bioavailability
The research confirmed that orally administered zeaxanthin reaches tumour tissues, with liquid chromatography-mass spectrometry detecting elevated levels in both blood plasma and tumour interstitial fluid of supplemented mice. This bioavailability supports the feasibility of dietary interventions.
Zeaxanthin occurs naturally in yellow corn, orange peppers, leafy greens, and egg yolks from corn-fed chickens. The compound is also widely available as a dietary supplement, primarily marketed for eye health due to its concentration in retinal tissue.
Future therapeutic development
The discovery opens new avenues for enhancing immunotherapy effectiveness through nutritional approaches. The researchers noted that their findings “uncover a previously unknown immunoregulatory function of ZEA, which has translational potential as a dietary element in bolstering immunotherapy.”
However, the study identified several limitations requiring further investigation. The precise mechanisms by which zeaxanthin alters cell membrane properties to enhance TCR clustering need clarification. Additionally, while CD4+ T cell depletion showed minimal effects on anti-tumour activity, the differential impacts on various T cell subsets warrant deeper analysis.
The research represents a significant advance in understanding diet-immune system interactions, demonstrating how specific food components can modulate complex cellular processes. As immunotherapy continues expanding across cancer types, dietary adjuvants like zeaxanthin could provide accessible means to enhance treatment outcomes.
Reference
Zhang, F. Q., Li, J., Zhang, R., et. al. (2025). Zeaxanthin augments CD8+ effector T cell function and immunotherapy efficacy. Cell Reports Medicine, 6, 102324. https://doi.org/10.1016/j.xcrm.2025.102324
