Taking these aspects into consideration and having previously reported the preferential uptake of PEG-EV by B16.F10 melanoma cells compared to LCL (Patras et al., 2021), we investigated whether in the case of our therapy the cytotoxic effects on tumor cells could be attributed to PEG-EV-DOX after abrogation of TAMs pro-tumor functions by IL-13-LCL-SIM. This evidence concerns the gene IL13 and melanoma.