Journal
BIOMATERIALS
Volume 222, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.119397
Keywords
gamma delta T cell; Selenium nanoparticles; Anti-Tumor immunity; alpha-Tubulin acetylation
Funding
- China Postdoctoral Science Foundation [2017M622898]
- Fundamental Research Funds for the Central Universities
- 111 project [B16021]
- Key Program of the National Natural Science Foundation of China [31830021]
- Natural Science Foundation of China [21877049]
- National Program for Support of Top-notch Young Professionals [W02070191]
- YangFan Innovative & Entrepreneur Research Team Project [201312H05]
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Immune cell therapy presents a paradigm for the treatment of malignant tumors. Human V gamma 9V delta 2 T cells, a subset of peripheral gamma delta T cells, have been shown to have promising anti-tumor activity. However, new methodology on how to achieve a stronger anti-tumor activity of V gamma 9V delta 2 T cells is under continuous investigation. In this work, we used selenium nanoparticles (SeNPs) to strengthen the anti-tumor cytotoxicity of V gamma 9V delta 2 T cells. We found SeNPs pretreated gamma delta T cells had significantly stronger cancer killing and tumor growth inhibition efficacy when compared with gamma delta T cells alone. Simultaneously, SeNPs pretreatment could significantly upregulate the expression of cytotoxicity related molecules including NKG2D, CD16, and IFN-gamma, meanwhile, downregulate PD-1 expression of gamma delta T cells. Importantly, we observed that SeNPs promoted tubulin acetylation modification in gamma delta 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 V gamma 9V delta 2 T cells, and both cytotoxicity related molecules and tubulin acetylation were involved in fine-tuning gamma delta T cell toxicity against cancer cells. Our present work demonstrated a new strategy for further enhancing anti-tumor cytotoxicity of human V gamma 9V delta 2 T cells by using SeNPs-based nanotechnology, not gene modification, implicating SeNPs-based nanotechnology had a promising clinical perspective in the gamma delta T cell immunotherapy for malignant tumors.
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