Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment
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 betwee...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.909880/full |
| _version_ | 1828466972910682112 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Raquel Lopes |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T03:59:25Z |
| format | Article |
| id | doaj.art-d196af56064e4460b728d59ff0ce7d5d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T03:59:25Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d196af56064e4460b728d59ff0ce7d5d2022-12-22T01:21:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.909880909880Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune MicroenvironmentRaquel Lopes0Raquel Lopes1Joana Caetano2Joana Caetano3Joana Caetano4Filipa Barahona5Filipa Barahona6Carolina Pestana7Carolina Pestana8Bruna Velosa Ferreira9Bruna Velosa Ferreira10Bruna Velosa Ferreira11Diana Lourenço12Diana Lourenço13Ana C. Queirós14Carlos Bilreiro15Carlos Bilreiro16Carlos Bilreiro17Noam Shemesh18Hans Christian Beck19Ana Sofia Carvalho20Rune Matthiesen21Bjarne Bogen22Bruno Costa-Silva23Karine Serre24Emilie Arnault Carneiro25Cristina João26Cristina João27Cristina João28Myeloma Lymphoma Research Group, Champalimaud Experimental Clinical Research Programme, Champalimaud Foundation, Lisbon, PortugalFaculty of Medicine, University of Lisbon, Lisbon, PortugalMyeloma Lymphoma Research Group, Champalimaud Experimental Clinical Research Programme, Champalimaud Foundation, Lisbon, PortugalHemato-Oncology Department, Champalimaud Foundation, Lisbon, PortugalFaculty of Medical Sciences, NOVA Medical School (NMS), Lisbon, PortugalMyeloma Lymphoma Research Group, Champalimaud Experimental Clinical Research Programme, Champalimaud Foundation, Lisbon, PortugalFaculty of Medical Sciences, NOVA Medical School (NMS), Lisbon, PortugalMyeloma Lymphoma Research Group, Champalimaud Experimental Clinical Research Programme, Champalimaud Foundation, Lisbon, PortugalCentre of Statistics and Its Applications, Faculty of Sciences, University of Lisbon, Lisbon, PortugalMyeloma Lymphoma Research Group, Champalimaud Experimental Clinical Research Programme, Champalimaud Foundation, Lisbon, PortugalHemato-Oncology Department, Champalimaud Foundation, Lisbon, PortugalFaculty of Medical Sciences, NOVA Medical School (NMS), Lisbon, PortugalMyeloma Lymphoma Research Group, Champalimaud Experimental Clinical Research Programme, Champalimaud Foundation, Lisbon, PortugalFaculty of Medicine, University of Coimbra, Coimbra, PortugalMyeloma Lymphoma Research Group, Champalimaud Experimental Clinical Research Programme, Champalimaud Foundation, Lisbon, PortugalFaculty of Medical Sciences, NOVA Medical School (NMS), Lisbon, PortugalNeural Plasticity and Neural Activity Laboratory, Champalimaud Experimental Clinical Research Programme, Champalimaud Foundation, Lisbon, PortugalRadiology Department, Champalimaud Foundation, Lisbon, PortugalNeural Plasticity and Neural Activity Laboratory, Champalimaud Experimental Clinical Research Programme, Champalimaud Foundation, Lisbon, PortugalCentre for Clinical Proteomics, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark0Computational and Experimental Biology, Chronic Diseases Research Centre (CEDOC); NOVA Medical School (NMS), Lisbon, Portugal0Computational and Experimental Biology, Chronic Diseases Research Centre (CEDOC); NOVA Medical School (NMS), Lisbon, Portugal1Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway2Systems Oncology, Champalimaud Physiology and Cancer Programme, Champalimaud Foundation, Lisbon, Portugal3Molecular Medicine Institute-Laço Hub, Instituto de Medicina Molecular João Lobo Antunes, Lisbon, PortugalMyeloma Lymphoma Research Group, Champalimaud Experimental Clinical Research Programme, Champalimaud Foundation, Lisbon, PortugalMyeloma Lymphoma Research Group, Champalimaud Experimental Clinical Research Programme, Champalimaud Foundation, Lisbon, PortugalHemato-Oncology Department, Champalimaud Foundation, Lisbon, PortugalFaculty of Medical Sciences, NOVA Medical School (NMS), Lisbon, PortugalMultiple 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.909880/fullMOPC315.BM cellsmultiple myelomamouse modeltumor immune microenvironmentextracellular vesicles |
| spellingShingle | 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 Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment Frontiers in Immunology MOPC315.BM cells multiple myeloma mouse model tumor immune microenvironment extracellular vesicles |
| title | Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment |
| title_full | Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment |
| title_fullStr | Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment |
| title_full_unstemmed | Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment |
| title_short | Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment |
| title_sort | multiple myeloma derived extracellular vesicles modulate the bone marrow immune microenvironment |
| topic | MOPC315.BM cells multiple myeloma mouse model tumor immune microenvironment extracellular vesicles |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.909880/full |
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