Frontiers in Immunology (Jul 2022)

Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment

  • Raquel Lopes,
  • Raquel Lopes,
  • Joana Caetano,
  • Joana Caetano,
  • Joana Caetano,
  • Filipa Barahona,
  • Filipa Barahona,
  • Carolina Pestana,
  • Carolina Pestana,
  • Bruna Velosa Ferreira,
  • Bruna Velosa Ferreira,
  • Bruna Velosa Ferreira,
  • Diana Lourenço,
  • Diana Lourenço,
  • Ana C. Queirós,
  • Carlos Bilreiro,
  • Carlos Bilreiro,
  • Carlos Bilreiro,
  • Noam Shemesh,
  • Hans Christian Beck,
  • Ana Sofia Carvalho,
  • Rune Matthiesen,
  • Bjarne Bogen,
  • Bruno Costa-Silva,
  • Karine Serre,
  • Emilie Arnault Carneiro,
  • Cristina João,
  • Cristina João,
  • Cristina João

DOI
https://doi.org/10.3389/fimmu.2022.909880
Journal volume & issue
Vol. 13

Abstract

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Multiple myeloma (MM), the third most frequent hematological cancer worldwide, is characterized by the proliferation of neoplastic plasma cells in the bone marrow (BM). One of the hallmarks of MM is a permissive BM microenvironment. Increasing evidence suggests that cell-to-cell communication between myeloma and immune cells via tumor cell-derived extracellular vesicles (EV) plays a key role in the pathogenesis of MM. Hence, we aimed to explore BM immune alterations induced by MM-derived EV. For this, we inoculated immunocompetent BALB/cByJ mice with a myeloma cell line, MOPC315.BM, inducing a MM phenotype. Upon tumor establishment, characterization of the BM microenvironment revealed the expression of both activation and suppressive markers by lymphocytes, such as granzyme B and PD-1, respectively. In addition, conditioning of the animals with MOPC315.BM-derived EV, before transplantation of the MOPC315.BM tumor cells, did not anticipate the disease phenotype. However, it induced features of suppression in the BM milieu, such as an increase in PD-1 expression by CD4+ T cells. Overall, our findings reveal the involvement of MOPC315.BM-derived EV protein content as promoters of immune niche remodeling, strengthening the importance of assessing the mechanisms by which MM may impact the immune microenvironment.

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