Zinc gluconate, a common zinc supplement, has made notable progress in research on anti-tumor immunity. The following details its roles in enhancing immune cell function, regulating immune factor secretion, and inhibiting tumor cell growth and metastasis:
I. Enhancement of Immune Cell Function
1. T Lymphocytes
T lymphocytes play a core role in anti-tumor immunity. Studies show that zinc gluconate promotes the proliferation and activation of T lymphocytes. Zinc ions influence the T cell receptor (TCR) signaling pathway, enhancing the ability of T cells to recognize and respond to antigens. For example, in animal experiments, supplementation with zinc gluconate increased the quantity and activity of CD4⁺ and CD8⁺ T cells in tumor-bearing mice, thereby enhancing the body’s specific killing effect on tumor cells.
Additionally, zinc gluconate regulates T cell differentiation, promoting the polarization of Th1 cells to enhance cellular immunity and inhibit tumor growth and metastasis.
2. Natural Killer (NK) Cells
NK cells are a critical component of the body’s innate immunity, capable of directly killing tumor cells. Zinc gluconate enhances the activity and cytotoxicity of NK cells. Research has found that zinc ions upregulate the expression of activating receptors on NK cell surfaces while downregulating inhibitory receptors, thereby enhancing NK cells’ recognition and killing of tumor cells.
In in vitro experiments, NK cells treated with zinc gluconate exhibit significantly increased cytotoxicity against multiple tumor cell lines.
3. Macrophages
Macrophages function in phagocytosing pathogens and tumor cells and play a key role in immune regulation. Zinc gluconate enhances macrophage phagocytosis, improving their ability to engulf tumor cells.
Meanwhile, zinc gluconate regulates macrophage polarization, promoting their differentiation into anti-tumor M1-type macrophages while inhibiting the pro-tumor M2-type polarization, thereby strengthening the body’s anti-tumor immune response.
II. Regulation of Immune Factor Secretion
1. Cytokines
Cytokines serve as critical mediators for communication and regulation between immune cells. Zinc gluconate modulates the secretion of multiple cytokines, including interleukin-2 (IL-2), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). These cytokines promote immune cell proliferation and activation, enhance immune cell cytotoxicity, and inhibit tumor growth and metastasis.
For example, IL-2 promotes the proliferation and activation of T cells and NK cells, strengthening anti-tumor immunity; IFN-γ has antiviral, anti-tumor, and immune-regulatory effects; TNF-α directly kills tumor cells and induces tumor cell apoptosis.
2. Chemokines
Chemokines attract immune cells to migrate directionally to tumor sites, enhancing local immune responses. Zinc gluconate regulates chemokine secretion, promoting immune cell infiltration into tumor tissues. For instance, it increases the expression of chemokines such as CCL5 and CXCL10, recruiting more T cells, NK cells, and other immune cells to tumor sites to exert anti-tumor effects.
III. Inhibition of Tumor Cell Growth and Metastasis
1. Induction of Tumor Cell Apoptosis
Zinc gluconate induces tumor cell apoptosis through multiple pathways. On one hand, it regulates the activity of apoptosis-related intracellular signaling pathways, such as activating the mitochondrial apoptosis pathway and death receptor pathway, to promote tumor cell apoptosis. On the other hand, zinc gluconate affects tumor cell metabolism, increasing intracellular reactive oxygen species (ROS) levels to induce oxidative stress and ultimately trigger apoptosis.
2. Inhibition of Tumor Angiogenesis
Tumor growth and metastasis depend on new blood vessels for nutrient and oxygen supply. Zinc gluconate inhibits the expression and activity of tumor angiogenesis-related factors, such as vascular endothelial growth factor (VEGF), thereby blocking tumor blood vessel formation, cutting off nutrient supply, and inhibiting tumor progression.
IV. Synergistic Effects with Other Treatments
1. Synergy with Chemotherapeutic Drugs
Studies have shown that combining zinc gluconate with chemotherapeutic agents enhances treatment efficacy while reducing adverse reactions. Zinc gluconate increases tumor cells’ sensitivity to chemotherapeutic drugs, promoting drug uptake and enhancing cytotoxicity. Additionally, it protects normal tissue cells from chemotherapeutic damage, mitigating adverse effects such as myelosuppression and gastrointestinal reactions.
2. Synergy with Immunotherapy
In immunotherapy, zinc gluconate can be used in conjunction with immune checkpoint inhibitors and adoptive cell therapy. It enhances overall immune function to improve treatment outcomes. For example, when combined with immune checkpoint inhibitors, zinc gluconate regulates the immune microenvironment, enhances T cell anti-tumor activity, and boosts the efficacy of checkpoint inhibitors.
