2. Academic Validation
  3. Identification and analysis of microplastic aggregation in CAR-T cells

Identification and analysis of microplastic aggregation in CAR-T cells

  • J Hazard Mater. 2024 Dec 5:480:136351. doi: 10.1016/j.jhazmat.2024.136351.
Zhao Yin 1,  Yizhen Huang 2,  Yangmin Zhu 2,  Qi Zhong 2,  Huijuan Shen 2,  Shaya Mahati 3,  Jing Huang 2,  Guangchao Li 2,  Ruiming Ou 4,  Zhi Liu 5,  Qing Zhang 6,  Shuang Liu 7
Affiliations

Affiliations

  • 1 Department of Hematology, Guangdong Second Provincial General Hospital, Jinan university, Guangzhou, Guangdong Province 510317, China. Electronic address: zhaoyin@stu2014.jnu.edu.cn.
  • 2 Department of Hematology, Guangdong Second Provincial General Hospital, Jinan university, Guangzhou, Guangdong Province 510317, China.
  • 3 Department of Tumor center, First Affiliated Hospital of Xinjiang Medical University, State key laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Centra Asia, Xinjiang Province 830054, China.
  • 4 Department of Hematology, Guangdong Second Provincial General Hospital, Jinan university, Guangzhou, Guangdong Province 510317, China. Electronic address: ouruiming@126.com.
  • 5 Department of Hematology, Guangdong Second Provincial General Hospital, Jinan university, Guangzhou, Guangdong Province 510317, China. Electronic address: liuzhi8112@126.com.
  • 6 Department of Hematology, Guangdong Second Provincial General Hospital, Jinan university, Guangzhou, Guangdong Province 510317, China. Electronic address: zhqing@vip.163.com.
  • 7 Department of Hematology, Guangdong Second Provincial General Hospital, Jinan university, Guangzhou, Guangdong Province 510317, China. Electronic address: Liush@gd2h.org.cn.
PMID: 39488976 DOI: 10.1016/j.jhazmat.2024.136351
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.

Keywords

Apoptosis; CAR-T cells; Ferroptosis; MTOR; Microplastics; T cell exhaustion.

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