Autor(es):
Lopes, Raquel ; Caetano, Joana ; Barahona, Filipa ; Pestana, Carolina ; Ferreira, Bruna Velosa ; Lourenço, Diana ; Queirós, Ana C. ; Bilreiro, Carlos ; Shemesh, Noam ; Beck, Hans Christian ; Carvalho, Ana Sofia ; Matthiesen, Rune ; Bogen, Bjarne ; Costa-Silva, Bruno ; Serre, Karine ; Carneiro, Emilie Arnault ; João, Cristina
Data: 2022
Identificador Persistente: http://hdl.handle.net/10362/142694
Origem: Repositório Institucional da UNL
Assunto(s): extracellular vesicles; MOPC315.BM cells; mouse model; multiple myeloma; tumor immune microenvironment; Immunology and Allergy; Immunology; SDG 3 - Good Health and Well-being
Descrição
Funding Information: This work was supported by Portuguese national funds, through FCT—Fundação para a Ciência e Tecnologia—in the context of the projects PDTC/MEC-HEM/30315/2017 and PCDC/MED-ONC/1215/2021, and by GILEAD GÉNESE (project PGG/058/2019). RL received a fellowship funded by FCT (2020.4875.BD). This work was also supported by the research infrastructure CONGENTO, co-financed by Lisboa Regional Operational Programme (Lisboa2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and FCT under the project LISBOA-01-0145-FEDER-022170. Fundings were not involved in the study design, collection, analysis, interpretation of data, writing of the article, or decision to submit it for publication.
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.
