Enhancing oncolytic virotherapy by extracellular vesicle mediated microRNA reprograming of the tumour microenvironment.

miRNA expression is critical in driving macrophage polarisation by simultaneously regulating expression of multiple cellular targets. Reintroducing miRNA to promote an anti-tumour macrophage phenotype is a promising therapeutic approach to reverse the immunosuppressive function of tumour associated macrophages.Small RNA sequencing was used to identify differentially expressed miRNA during TAM generation and following LPS/IFNγ stimulation to induce an anti-tumour phenotype. Two differentially expressed miRNA identified, miR-155 and miR-19a, were cloned into oncolytic rhabdovirus (ORV), and anti-tumour efficacy was investigated using both in vitro and in vivo models of OvCa. To identify miRNA that are dysregulated during pro-tumour and anti-tumour TAM polarisation, we performed small RNA sequencing on in vitro SKOV-3 generated TAMs ± LPS/IFNg and autologous monocytes from four healthy donors.