The immunosuppressive role of HLA-G+ extracellular vesicles in bone marrow of infiltrating tumors: The lesson learned from neuroblastoma and multiple myeloma.

It is now clearly established that extracellular vesicles (EV)s represent important players in the regulation of bone marrow (BM) microenvironment during cancer progression, and anti-tumor responses. Indeed, healthy cells and neoplastic cells crosstalk through a dynamic transfer of extracellular vesicles in the tumor microenvironment including the BM. The mechanisms underlying reflect the peculiar features of EVs that carry bioactive cargo like proteins and non-coding RNAs on short and long distance to reprogram tumor microenvironment and modulate the immune response. In this context, we and others reported that tumor-derived EVs are equipped on the surface with immune-checkpoint and immunosuppressive molecules such as HLA-G. These EVs are often associated with disease progression, tumor metastases, and poor clinical outcome and their role in neuroblastoma (NB) and multiple myeloma (MM) is here reported. Although NB and MM are very different tumors in terms of origin and age of diagnosis, they share the common feature that grow up into the BM causing a dysregulation of the BM microenvironment. EVs take part in this process.