Tumor extracellular vesicles loaded with exogenous Let-7i and miR-142 can modulate both immune response and tumor microenvironment to initiate a powerful anti-tumor response. (31st March 2021)

• Record Type: Journal Article
• Authors: Khani, Adeleh Taghi; Sharifzad, Farzaneh; Mardpour, Soura; Hassan, Zuhair Mohammad; Ebrahimi, Marzieh
• Is Part Of: Cancer letters. Volume 501(2021)
• Page Start: 200
• Page End: 209
• Publication Date: 2021-03-31
• Subjects: Tumor-derived extracellular vesicles -- miRNA -- Dendritic cell maturation and T cell activation; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2020.11.014
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Despite recent advances in cancer immunotherapy, there have been limitations in cancer treatment and patient survival due to a lack of antigen recognition and immunosuppressive tumor microenvironment. To overcome this issue, we have shown that miRNA modified tumor-derived Extracellular Vesicles (mt-EVs) would be an advantageous prospect since they are tumor specific and associated antigen sources which cause increase in maturation and antigen-presenting function of dendritic cells. Also, miRNAs are promising candidates for cancer therapy because of their ability to control several host immune subsets to respond against cancer cells as well as tumor microenvironment remodeling. Here, we report that mt-EVs containing tumor specific antigens loaded with miRNAs (Let-7i, miR-142 and, miR-155) could increase the survival rate of tumor-bearing mice and induce reduction in tumor growth. Importantly, the administration of mt-EVs elicited cytotoxic T cells with increasing in IFNγ and Granzyme B production ability. Notably, intramuscular (IM) injection of let7i, miR142-EVs had a significant effect on dendritic cell (DC) maturation and T cell activation along with tumor shrinkage. Collectively, our findings suggest that administration of miRNA containing EVs may be effective immunotherapy against solid tumors. Highlights: Non-Cellular Immunotherapy may provide new improvement in cancer treatment. Tumor-derived extracellular vesicles are source of tumor antigens as well as vehicles for targeting tumor microenvironment. Dendritic cells are important mediators of innate and adaptive immune system.