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Published on: February 27, 2019
Identification and analysis of microplastic aggregation in CAR-T cells
Zhao Yin1, Yizhen Huang1, Yangmin Zhu1
1Department of Hematology, Guangdong Second Provincial General Hospital, Jinan university, Guangzhou, Guangdong Province 510317, China.
Abstract:
Microplastics (MPs) are increasingly recognized as contaminants present in various environments and are widely acknowledged as potential hazards to the mammalian immune system. In our study of chimeric antigen receptor T cell (CAR-T) therapy, we observed the presence of MP in CAR-T cell products for the first time. It is worth exploring whether MP could enter CAR-T cells and how they might affect CAR-T cells' functionality. Therefore, we analyzed how MP affected CD19 and BCMA-CAR-T cells. Based on flow cytometry, ELISA, and cytotoxicity analysis of in vitro and in vivo experiments, MP suppressed the activity of CAR-T cells. Subsequent investigation revealed that the exposure of CAR-T cells to varying concentrations of MP resulted in a notable increase in apoptosis, ferroptosis, and exhaustion levels. Furthermore, the hyperactivation of the mTOR signaling pathway in MP-treated CAR-T cells was verified. The partial restoration of CAR-T cell function in MP was achieved by inhibiting the mTOR pathway. MP present a threat to CAR-T cell function due to their role in inducing CAR-T cell apoptosis, ferroptosis, and T-cell exhaustion through the hyperactivation of mTOR signaling pathways.
Insights
Microplastics (MPs) contaminate chimeric antigen receptor T cell (CAR-T) products, suppressing their anti-cancer activity. MPs induce apoptosis, ferroptosis, and exhaustion in CAR-T cells by hyperactivating mTOR signaling.
Area of Science:
- Immunology
- Environmental Science
- Biotechnology
Background:
- Microplastics (MPs) are emerging environmental contaminants with potential adverse effects on mammalian immune systems.
- Chimeric antigen receptor T cell (CAR-T) therapy is a promising cancer treatment, but its efficacy may be compromised by environmental factors.
- The presence of MPs in CAR-T cell products was observed for the first time, necessitating an investigation into their impact.
Purpose of the Study:
- To investigate the effects of microplastics (MPs) on the functionality of CD19 and BCMA-CAR-T cells.
- To determine the mechanisms by which MPs affect CAR-T cell activity, including apoptosis, ferroptosis, and exhaustion.
- To explore potential therapeutic strategies to mitigate MP-induced impairment of CAR-T cell function.
Main Methods:
- In vitro and in vivo experiments were conducted using CD19 and BCMA-CAR-T cells.
- Flow cytometry, ELISA, and cytotoxicity assays were employed to assess CAR-T cell activity.
- Analysis of apoptosis, ferroptosis, T-cell exhaustion markers, and mTOR signaling pathway activation was performed.
Main Results:
- Microplastics (MPs) were found to suppress the activity of CAR-T cells.
- Exposure to MPs significantly increased apoptosis, ferroptosis, and exhaustion levels in CAR-T cells.
- MP exposure led to hyperactivation of the mTOR signaling pathway in CAR-T cells.
Conclusions:
- Microplastics (MPs) pose a significant threat to CAR-T cell function, impairing their anti-cancer efficacy.
- MPs induce CAR-T cell apoptosis, ferroptosis, and exhaustion via hyperactivation of mTOR signaling.
- Inhibiting the mTOR pathway partially restored CAR-T cell function in the presence of MPs, suggesting a potential therapeutic target.
