Vitamin CNEW2026

Vitamin C enhances cytotoxicity of CAR-and εTRuC-engineered γδ T cells and modulates Ca, NFAT, NF-κB and ERK signaling in human γδ T cells.

Zarobkiewicz Michal, Ma Lin, Juraske Claudia, Cierna Lea et al. — Frontiers in immunology

Summary

This study suggests that vitamin C can boost the ability of specific immune cells, called gamma-delta T cells, to kill cancer cells. Researchers found that vitamin C enhances these cells' cancer-fighting power and influences their internal communication pathways. These findings indicate a potential role for vitamin C in supporting the body's immune responses against cancer.

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Key points

Vitamin C can enhance the cancer-killing ability of specific immune cells called gamma-delta T cells.
It appears to do this by influencing key internal signaling pathways within these immune cells.
These findings suggest vitamin C might play a supportive role in the body's immune defense against cancer.

What the study looked at

What question the study asked: Researchers wanted to understand if and how vitamin C affects the ability of a specific type of immune cell, called gamma-delta T cells, to fight cancer. While these cells are known for their anti-cancer potential, scientists are looking for ways to make them even more effective. How it was studied (design/participants): This laboratory study examined human gamma-delta T cells, including some that were genetically modified (CAR- and εTRuC-engineered) to target cancer more specifically. The researchers treated these cells with vitamin C and then observed their ability to kill cancer cells and analyzed changes in their internal signaling pathways. What it found: The study found that vitamin C significantly boosted the cancer-killing power of both unmodified and engineered gamma-delta T cells. This enhancement was linked to increased production of certain immune molecules and changes in several internal cellular communication pathways, such as calcium influx and the activity of NFAT, NF-κB, and ERK proteins. These results suggest vitamin C directly influences the function of these important immune cells.

Dietary takeaway

While this laboratory study shows vitamin C can enhance immune cell function, it's important to remember that these findings are from a controlled environment and not from human trials. Eating a balanced diet rich in vitamin C from fruits and vegetables like oranges, strawberries, bell peppers, and broccoli is always beneficial for overall health and immune support. However, we cannot conclude from this single study that vitamin C supplements or high doses will prevent or treat cancer in humans.

Abstract

γδ T cells have raised interest as effector cells in cancer immunotherapy, due to their broad and HLA-independent reactivity towards multiple tumor entities. Despite promising ongoing clinical studies, there is a need to improve the effector function and thereby the efficacy of γδ T cells. In addition to its role as anti-oxidant, Vitamin C is an epigenetic modifier and exerts multiple effects on T-cell differentiation. While Vitamin C enhances proliferation, cytokine production and cytotoxicity of γδ T cells, the associated signaling pathways have so far not been elucidated. Here we demonstrate that Vitamin C enhances the cytotoxic effector function of unmodified as well as anti-CD19 chimeric antigen receptor (CAR) and TCR fusion construct (εTRuC)-transduced zoledronate-expanded γδ T cells. This was associated with increased upregulation of CD25 and IFN-γ secretion. Vitamin C increased calcium influx and nuclear translocation of NFAT and NF-κB in short-term expanded γδ T-cell lines. Although Vitamin C did not alter CD3ζ phosphorylation following stimulation with anti-CD3 antibodies, it reduced phosphorylation of ERK1/2 without affecting p38 MAP kinases. Further analysis showed that Vitamin C did not modulate the expression of selected immune checkpoint molecules on γδ T cells. Our results identify important signaling events where Vitamin C enhances the effector activity of human γδ T cells.

View on PubMed →DOI: 10.3389/fimmu.2026.1759941