Exosomes from CIITA-Transfected CT26 Cells Enhance AntitumorEffects

Abstract

Aim: To study anti-tumor effects of exosomes from class II transactivator (CIITA) gene transfected CT26cells. <br/><b>Methods</b>: In this study, we established an MHC class II molecule-expressing murine colon cancer cellline (CT26-CIITA) by transduction of the CIITA gene. Immune effects in vitro and tumor protective results invivo were tested and monitored. <br/><b>Results</b>: Exosomes from CT26-CIITA cells were found to contain a high levelof MHC class II protein. When loaded on dendritic cells (DCs), exosomes from CT26-CIITA cells significantlyincreased expression of MHC class II molecules, CD86 and CD80, as compared to exosomes from CT26 cells.In vitro assays using co-culture of immunized splenocytes and exosome-loaded DCs demonstrated that CIITAExoenhanced splenocyte proliferation and IFN-γ production of CD4+T cells, while inhibiting IL-10 secretion.In addition, compared to exosomes from CT26 cells, CT26-CIITA-derived exosomes induced higher TNF-α andIL-12 mRNA levels. A mouse tumour preventive model showed that CT26-CIITA derived exosomes significantlyinhibited tumour growth in a dose-dependent manner and significantly prolonged the survival time of tumourbearingmice. <br/><b>Conclusion</b>: Our findings indicate that CT26-CIITA-released exosomes are more efficient to induceanti-tumour immune responses, suggesting a potential role of MHC class II-containing tumour exosomes ascancer vaccine candidates.