Chitosan Nanoparticles Strengthen Vγ9Vδ2 T-Cell Cytotoxicity Through Upregulation Of Killing Molecules And Cytoskeleton Polarization

Background: During the past few years, immune cell therapy for malignant cancer has benefited a considerable amount of patients worldwide. As one of several promising candidates for immunotherapy, V gamma 9V delta 2 gamma delta T cells have many unique biological advantages, such as non-MHC restriction and have been noted as the earliest source of IFN-gamma. However, potentiating anti-tumor functions of gamma delta T cells has become of particular interest to researchers studying gamma delta T cell applications. Purpose: In this study, we proposed a nanotechnology-based methodology for strengthening gamma delta T cell functions. Methods: As a type of reliable, biocompatible material, chitosan nanoparticles (CSNPs) were used to enhance anti-tumor immunity of gamma delta T cells. Results: First, we found that the size of prepared CSNPs distributed 50 to 100 nm, and that CSNPs had optimal immunocompatibility. Then, we observed that CSNPs could induce alpha-tubulin cytoskeleton polarization and rearrangement, correlating with a higher killing ability of gamma delta T cells. Furthermore, we revealed that CSNPs could enhance V gamma 9V delta 2 T cell anti-tumor functions by upregulating killing of related receptors, including NKG2D, CD56, FasL, and perforin secretion. Conclusion: Our work provided evidence of application for CSNPs based bio-carrier in immunotherapy. More importantly, we proposed a new strategy for enhancing gamma delta T cell antitumor activity using nanobiomaterial, which could benefit future clinical applications of gamma delta T cells.