Dataset Information

Multiple myeloma-derived extracellular vesicles modulate the bone marrow immune microenvironment

ABSTRACT: One of the hallmarks of multiple myeloma (MM) is a permissive BM microenvironment. Increasing evidence suggest 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Bone Marrow, Bone Marrow Cell

DISEASE(S): Multiple Myeloma

SUBMITTER: Rune Matthiesen

LAB HEAD: Rune Matthiesen

PROVIDER: PXD032934 | Pride | 2022-07-05

REPOSITORIES: Pride

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Publications

The Immune Microenvironment in Multiple Myeloma: Friend or Foe?

Lopes Raquel R Caetano Joana J Caetano Joana J Ferreira Bruna B Barahona Filipa F Carneiro Emilie Arnault EA João Cristina C

Cancers 20210205 4

Multiple myeloma (MM) is one of the most prevalent hematological cancers worldwide, characterized by the clonal expansion of neoplastic plasma cells in the bone marrow (BM). A combination of factors is implicated in disease progression, including BM immune microenvironment changes. Increasing evidence suggests that the disruption of immunological processes responsible for myeloma control ultimately leads to the escape from immune surveillance and resistance to immune effector function, resulting ...[more]

PMID: 33562441

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Project description:Although the "seed and soil" hypothesis was proposed by Stephen Paget at the end of the 19th century, where he said that tumor cells (seeds) need a propitious medium (soil) to be able to establish metastases, only recently the tumor microenvironment started to be more studied in the field of Oncology. Multiple myeloma (MM), a malignancy of plasma cells, can be considered one of the types of cancers where there is more evidence in the literature of the central role that the bone marrow (BM) microenvironment plays, contributing to proliferation, survival, migration and drug resistance of tumor cells. Despite all advances in the therapeutic arsenal for MM treatment in the last years, the disease remains incurable. Thus, studies aiming a better understanding of the pathophysiology of the disease, as well as searching for new therapeutic targets are necessary and welcome. Therefore, the present study aimed to evaluate the protein expression profiling of mononuclear cells derived from BM of MM patients in comparison with these same cell types derived from healthy individuals, in order to fill this gap in MM treatment. Proteomic analysis was performed using the mass spectrometry technique and further analyses were done using bioinformatics tools, to identify dysregulated biological pathways and/or processes in the BM microenvironment of patients with MM as a result of the disease. Among the pathways identified in this study, we can highlight an upregulation of proteins related to protein biosynthesis, especially chaperone proteins, in patients with MM. Additionally, we also found an upregulation of several proteins involved in energy metabolism, which is one of the cancer hallmarks. Finally, with regard to the downregulated proteins, we can highlight mainly those involved in different pathways of the immune response, corroborating the data that has demonstrated that the immune system of MM is impaired and, therefore, the immunotherapies that have been studied recently for the treatment of the disease are extremely necessary in the search for a control and a cure for these patients who live with the disease.

			Action	DRS
	Bag7_BM1_1_1.raw	Raw
	Bag7_BM1_1_1_MSMS.mgf	Mgf
	Bag7_BM1_1_1_PepInfo.txt	Txt
	Bag7_BM1_1_2.raw	Raw
	Bag7_BM1_1_2_MSMS.mgf	Mgf