Journal Article

Effects of functional antioxidants on the expansion of gamma delta T-cells and their cellular cytotoxicity against bladder cancer cells

Pan, Yueh, Shih, Ping-Hsiao, Hsiao, Chi-Hao, Chiu, Ya-Hsu, Shih, Hung-Jen, Chang, Chin-Pao, Lin, Chi-Chen, Chuang, Shu-Han, Wang, Pai-Fu

2025

Overview

Purpose Results of previous studies have demonstrated that T-cell receptor cross-linking rapidly generates reactive oxygen species, which play essential signaling roles within mitochondria for the antigen-specific expansion of T-cells. However, oxidative stress also causes damage to cellular organelles. Thus, modulating ROS metabolism using antioxidants during naïve T-cell activation may promote the expansion and generation of functional T-cells. Notably, urothelial cancer is a sex-specific malignancy with high mortality rates worldwide. The present study aimed to evaluate the effects of various antioxidants on γδ T-cell proliferation, and the associated cytotoxicity against urothelial carcinoma cells (UCs). Methods Over a period of cell induction and expansion, peripheral blood mononuclear cells were cultured with or without different antioxidants, including N -acetyl cysteine (NAC), vitamin C and vitamin E. Subsequently, phenotypic characterization of γδ T-cells and their cytolytic effects against UCs were analyzed by flow cytometry and cell viability assays, respectively. Results and Conclusions The results revealed that NAC partially inhibited T-cell expansion in a dose-dependent manner. In addition, CD3 + /Vγ9 + levels and natural killer group 2D receptor expression were mildly reduced following treatment with a high dose of NAC, whereas CD3 + /CD56 + levels and CD314 expression in natural killer-like cells were moderately decreased following treatment with vitamin E. Particularly, the direct co-incubation of bladder cancer cells with γδ T-cells supplemented with antioxidants significantly enhanced bladder cancer cytolysis. Collectively, results of the present study revealed that co-administration of functional antioxidants during γδ T-cell expansion may enhance the quality and efficacy of adoptive T-cell therapies for cancer treatment.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acetylcysteine / Acetylcysteine - pharmacology / Adoptive T-cell therapy / Antibodies / Antioxidants / Antioxidants - pharmacology / Ascorbic acid / Ascorbic Acid - pharmacology / Biomedical and Life Sciences / Biomedicine / Bladder cancer / Cancer Research / Cancer therapies / Care and treatment / CD3 antigen / CD56 antigen / Cell activation / Cell death / Cell Line, Tumor / Cell proliferation / Cell Proliferation - drug effects / Cell Survival - drug effects / Cell therapy / Cell viability / Cystectomy / Cytolysis / Cytotoxicity / Cytotoxicity, Immunologic - drug effects / Diagnosis / Dosage and administration / Enzymes / Flow cytometry / Health aspects / Health Promotion and Disease Prevention / Humans / Intraepithelial Lymphocytes - drug effects / Intraepithelial Lymphocytes - immunology / Leukocytes (mononuclear) / Ligands / Lymphocyte Activation - drug effects / Lymphocytes / Lymphocytes T / Malignancy / Medicine/Public Health / Metastasis / Multi-functional antioxidant / Natural killer cells / Oncology / Organelles / Oxidative stress / Oxidative Stress - drug effects / Patient outcomes / Peripheral blood mononuclear cells / Reactive oxygen species / Reactive Oxygen Species - metabolism / Receptors, Antigen, T-Cell, gamma-delta - immunology / Receptors, Antigen, T-Cell, gamma-delta - metabolism / Statistical analysis / Surgical Oncology / T cell receptors / T-Lymphocytes - drug effects / T-Lymphocytes - immunology / Tumors / Urinary Bladder Neoplasms - drug therapy / Urinary Bladder Neoplasms - immunology / Urinary Bladder Neoplasms - metabolism / Urinary Bladder Neoplasms - pathology / Urothelial cancer / Urothelial carcinoma of the bladder / Vitamin C / Vitamin E / Vitamin E - pharmacology / Zoledronic acid / Γδ T-cell