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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Immunological Tolerance and Regulation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1469771

Immunomodulatory properties of extracellular vesicles isolated from bone marrow of patients with neuroblastoma: role of PD-L1 and HLA-G

Provisionally accepted
Danilo Marimpietri Danilo Marimpietri 1Maria V. Corrias Maria V. Corrias 2Gino Tripodi Gino Tripodi 3Roberto Gramignoli Roberto Gramignoli 1Irma Airoldi Irma Airoldi 1Fabio Morandi Fabio Morandi 1*
  • 1 Laboratory of Cellular Therapies, Giannina Gaslini Institute (IRCCS), Genoa, Italy
  • 2 Laboratory of Experimental Therapies in Oncology, Giannina Gaslini Institute (IRCCS), Genova, Italy
  • 3 Department of Immunology and Transfusion medicine, Giannina Gaslini Institute (IRCCS), Genoa, Italy

The final, formatted version of the article will be published soon.

    Extracellular vesicles (EVs) can be released by any cell and are crucial for cell-to-cell communications. EVs have been characterized in patients with solid and hematological tumors, where they play an important role in tumor progression and metastasis. EVs may express different surface proteins derived from the parental cells, including immunomodulatory molecules, such as HLA-G and PD-L1. We found a higher expression of CD56 on EVs derived from bone marrow (BM) of patients with neuroblastoma (NB) than in those from healthy donors (HD). However, CD56 expression was not dependent on BM infiltration of NB cells. Moreover, the analysis of GD2 expression revealed that only a small fraction of EVs was released by infiltrating NB cells, whereas the majority may derive from BM-resident cells. BM-derived EVs from NB patients display a higher expression of HLA-G and PD-L1 than those derived from HD. Nonetheless, such EVs are able to modulate T cell immune responses. We measured a robust response, in vitro, towards a common bacterial antigen, including the release of GM-CSF and pro-inflammatory cytokines, like IFN-α and IL-6, from mononuclear cells. Some of these immunomodulatory features are dependent on the expression of HLA-G and PD-L1, whereas others may rely on other mechanism(s). Finally, a high expression of CD56, HLA-G and PD-L1 on BM-derived EVs may represent a good prognostic factor. In conclusion, we described the presence of HLA-G and PD-L1-bearing EVs in the BM of NB patients, which may represent a mechanism performed by resident BM cells to counteract the inflammation occurring in the BM microenvironment of NB patients.

    Keywords: Neuroblastoma, extracellular vesicles, HLA-G, PD-L1, Bone Marrow

    Received: 24 Jul 2024; Accepted: 03 Oct 2024.

    Copyright: © 2024 Marimpietri, Corrias, Tripodi, Gramignoli, Airoldi and Morandi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Fabio Morandi, Laboratory of Cellular Therapies, Giannina Gaslini Institute (IRCCS), Genoa, Italy

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