Selenium nanoparticles as new strategy to potentiate γδ T cell anti-tumor cytotoxicity through upregulation of tubulin-α acetylation.

Abstract

Immune cell therapy presents a paradigm for the treatment of malignant tumors. Human Vγ9Vδ2 T cells, a subset of peripheral γδ T cells, have been shown to have promising anti-tumor activity. However, new methodology on how to achieve a stronger anti-tumor activity of Vγ9Vδ2 T cells is under continuous investigation. In this work, we used selenium nanoparticles (SeNPs) to strengthen the anti-tumor cytotoxicity of Vγ9Vδ2 T cells. We found SeNPs pretreated γδ T cells had significantly stronger cancer killing and tumor growth inhibition efficacy when compared with γδ T cells alone. Simultaneously, SeNPs pretreatment could significantly upregulate the expression of cytotoxicity related molecules including NKG2D, CD16, and IFN-γ, meanwhile, downregulate PD-1 expression of γδ T cells. Importantly, we observed that SeNPs promoted tubulin acetylation modification in γδ T cells through interaction between microtubule network and lysosomes since the latter is the primary resident station of SeNPs shown by confocal visualization. In conclusion, SeNPs could significantly potentiate anti-tumor cytotoxicity of Vγ9Vδ2 T cells, and both cytotoxicity related molecules and tubulin acetylation were involved in fine-tuning γδ T cell toxicity against cancer cells. Our present work demonstrated a new strategy for further enhancing anti-tumor cytotoxicity of human Vγ9Vδ2 T cells by using SeNPs-based nanotechnology, not gene modification, implicating SeNPs-based nanotechnology had a promising clinical perspective in the γδ T cell immunotherapy for malignant tumors.

• Authors: Yi Hu, Ting Liu, Jingxia Li, Fengyi Mai, Jiawei Li, Yan Chen, Yanyun Jing, Xin Dong, Li Lin, Junyi He, Yan Xu, Changliang Shan, Jianlei Hao, Zhinan Yin, Tianfeng Chen, Yangzhe Wu
• Journal: Biomaterials (Biomaterials) Vol. 222 Pg. 119397 (11 2019) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 31442884 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Antineoplastic Agents
• KLRK1 protein, human
• NK Cell Lectin-Like Receptor Subfamily K
• Receptors, IgG
• Tubulin
• Selenium

Topics

• Acetylation
• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Humans
• Mice
• NK Cell Lectin-Like Receptor Subfamily K (metabolism)
• Nanoparticles (chemistry)
• Nanotechnology
• Receptors, IgG (metabolism)
• Selenium (chemistry)
• Tubulin (metabolism)