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

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.