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Moscvin, Maria, Evans, Benjamin 
ORCID: https://orcid.org/0000-0001-6849-9758 and Bianchi, Giada
(2023)
Dissecting molecular mechanisms of immune microenvironment dysfunction in multiple myeloma and precursor conditions.
Journal of Cancer Metastasis and Treatment, 9.
ISSN 2394-4722
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Abstract
Multiple myeloma (MM) is a disease of clonally differentiated plasma cells. MM is almost always preceded by precursor conditions, monoclonal gammopathy of unknown significance (MGUS), and smoldering MM (SMM) through largely unknown molecular events. Genetic alterations of the malignant plasma cells play a critical role in patient clinical outcomes. Del(17p), t(4;14), and additional chromosomal alterations such as del(1p32), gain(1q) and MYC translocations are involved in active MM evolution. Interestingly, these genetic alterations appear strikingly similar in transformed plasma cell (PC) clones from MGUS, SMM, and MM stages. Recent studies show that effectors of the innate and adaptive immune response show marked dysfunction and skewing towards a tolerant environment that favors disease progression. The MM myeloid compartment is characterized by myeloidderived suppressor cells (MDSCs), dendritic cells as well as M2-like phenotype macrophages that promote immune evasion. Major deregulations are found in the lymphoid compartment as well, with skewing towards immune tolerant Th17 and Treg and inhibition of CD8+ cytotoxic and CD4+ activated effector T cells. In summary, this review will provide an overview of the complex cross-talk between MM plasma cells and immune cells in the microenvironment and the molecular mechanisms promoting progression from precursor states to full-blown myeloma.
| Item Type: | Article |
|---|---|
| Additional Information: | Publisher Copyright: © The Author(s) 2023. |
| Uncontrolled Keywords: | immune response,immune-microenvironment,immunotherapy,multiple myeloma,plasma cells,oncology ,/dk/atira/pure/subjectarea/asjc/2700/2730 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 10 Aug 2026 09:48 |
| Last Modified: | 10 Aug 2026 09:48 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/104063 |
| DOI: | 10.20517/2394-4722.2022.110 |
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