Therapeutic Exosomal Vaccine for Enhanced Cancer Immunotherapy by Mediating Tumor Microenvironment

Tumor immunotherapy has been convincingly demonstrated as a feasible approach for treating cancers. Although promising, however, the immunosuppressive tumor microenvironment (TME) has been recognized as a major obstacle in tumor immunotherapy. It is highly desirable to release an immunosuppressive “brake” for improving cancer immunotherapy. Among tumor-infiltrated immune cells, tumor-associated macrophages (TAMs) play an important role in the growth, invasion and metastasis of tumors. The polarization of TAMs (M2) into the M1 type can alleviate the immunosuppression of the TME and enhance the effect of immunotherapy. Inspired by this, we constructed a therapeutic exosomal vaccine from antigen-stimulated M1-type macrophages (M1OVA-Exos). M1OVA-Exos are capable of polarizing TAMs into M1 type through downregulation of the Wnt signaling pathway. Mediating the TME further activates the immune response and inhibits tumor growth and metastasis via the exosomal vaccine. Our study provides a new strategy for the polarization of TAMs, which augments cancer vaccine therapy efficacy. Overall design: To explore the mechanism by which M1-Exos polarizes macrophages of the M1 phenotype, the micRNA of M0-Exos and M1-Exos were extracted, and this micRNA was sequenced. The target genes of different strands of micRNA were found, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed on them to explore the relevant signaling pathways.