Tumor-Derived Exosomes Enriched by miRNA-211a Promote Antitumor Immune Response in B16F10 Tumor-Bearing Mice

Abstract

Tumor-associated antigens that can induce antitumor immune responses as well as endogenous microRNAs are found in tumor-derived exosomes (TEXs). The objective of the current investigation was to assess the ability of MicroRNA (miR)-211-enriched TEX (TEXomiR) to induce antitumor immune responses in a melanoma mouse model. B16F10 melanoma cells in culture were used to extract exosomes. MiR-211 mimics were introduced into the exosomes using a modified calcium chloride technique. In C57BL/6 mice, the effects of TEXomiR were assessed by measuring tumor growth, weight, immune cell populations in the tumor and spleen and cytokine release. PBS, TEX, or TEXomiR were given subcutaneously to mice three times every 3 days until tumors grew to a size of 100 mm³. In vivo experiments using B16F10-bearing mice indicated that, in comparison with unmodified TEX and PBS, TEXomiR administration boosted improved antitumor immune responses. There was a notable increase in survival time. Mice treated with TEXomiR showed suppression of tumor development. Tumor tissue had much lower ratios of T regularity/CD8 T cells and CD4/CD8 T cells. Our findings showed that TEXomiR stimulates antitumor immune responses and that tumor-derived exosomes are an effective vehicle for miR-211 mimic delivery.