Related Experiment Video
Updated: Aug 5, 2026
10:09
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Extracellular Vesicles as Master Regulators of Immune Modulation in Multiple Myeloma
Marzia Pucci1, Elisa Costanzo1,2, Martina Marfia1
1Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Via Divisi 83, 90133 Palermo, Italy.
International Journal of Molecular Sciences
|July 28, 2026
Summary
Multiple myeloma involves immune evasion via dysregulated immune checkpoints and extracellular vesicles (EVs). Targeting these pathways and using EVs offers new precision medicine strategies for this plasma cell malignancy.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Multiple myeloma (MM) is a heterogeneous plasma cell cancer originating in the bone marrow.
- Progression from monoclonal gammopathy of undetermined significance (MGUS) to smouldering multiple myeloma (SMM) involves genetic alterations.
- Immune checkpoints (e.g., PD-1, CTLA-4) are crucial in the immunosuppressive bone marrow microenvironment, leading to T-cell dysfunction and therapeutic resistance.
Purpose of the Study:
- To review the role of immune checkpoint dysregulation in multiple myeloma pathogenesis.
- To explore the function of extracellular vesicles (EVs) in MM-mediated immune suppression and tumor progression.
- To discuss the therapeutic potential of targeting immune checkpoints and utilizing EVs in MM.
Main Methods:
- Literature review of immune checkpoint pathways in MM.
- Analysis of extracellular vesicle (EV) cargo and function in the MM microenvironment.
- Synthesis of current research on therapeutic strategies targeting immune checkpoints and EVs.
Main Results:
- Dysregulated immune checkpoint receptors (PD-1, CTLA-4, TIM-3, LAG-3, CD47) promote T-cell exhaustion and immune evasion in MM.
- MM-derived EVs carry bioactive molecules that reprogram immune and stromal cells, fostering tumor progression and immune escape.
- EVs can carry immune checkpoint molecules, contributing to a permissive tumor microenvironment.
Conclusions:
- Immune checkpoint dysregulation and EV-mediated immunomodulation are key drivers of multiple myeloma progression.
- Targeting immune checkpoints and leveraging EVs present promising avenues for novel MM therapies.
- EVs hold potential as biomarkers and drug delivery systems for advancing precision medicine in MM.
More Related Videos
Related Concept Videos
01:36Overview of Exosomes
Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
01:19Mesenchymal Stem Cells
Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their access...
01:15Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
01:38Intralumenal Vesicles and Multivesicular Bodies
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
01:33Overview of Secretory Vesicles
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
02:17The Tumor Microenvironment
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...