Exosomes and immune modulation: implications for neuroblastoma immunotherapy

Exosomes are nano-sized extracellular vesicles involved in cell homeostasis. Tumor-derived exosomes (TDEs) promote tumor progression by creating an immunosuppressive tumor microenvironment (TME), inhibiting T and NK cell activity, preventing dendritic cell maturation, and expanding immunosuppressive cell populations. Cancer Stem Cell (CSC)-derived exosomes further trigger functional changes in immune cells subsets, enhancing immune suppression. Consequently, blocking the release or the uptake of TDEs significantly impact immunotherapy efficacy, making them potential therapeutic targets. On the other hand, NK cell-derived exosomes can be engineered to carry immune-activating molecules or inhibitors of immune checkpoint molecules to elicit immune responses. This review highlights the interplay between TDEs and immune cells, particularly NK cells, in different tumors, with a focus on neuroblastoma, and explores exosome-based strategies to improve immunotherapy efficacy.