Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities

Multiple myeloma (MM) is the second most common hematologic malignancy, characterized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often throug...

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Bibliographic Details
Published in:Cancers 2021-06, Vol.13 (13), p.3213
Main Authors: Botta, Cirino, Mendicino, Francesco, Martino, Enrica Antonia, Vigna, Ernesto, Ronchetti, Domenica, Correale, Pierpaolo, Morabito, Fortunato, Neri, Antonino, Gentile, Massimo
Format: Article
Language:English
Subjects:
Adaptive immunity
Angiogenesis
Antigens
Apoptosis
Benign monoclonal gammopathy
Bone marrow
Cancer therapies
Dendritic cells
Disease
Disease resistance
Drug resistance
Drugs
Epigenetics
Evolution
Immune evasion
Immune system
Immunomodulation
Immunosuppressive agents
Immunotherapy
Inflammation
Lymphocytes
Malignancy
Medical prognosis
Microbiota
Microenvironments
Molecular modelling
Monoclonal antibodies
Multiple myeloma
Neutrophils
Patients
Phenotypes
Review
Thalidomide
Tumors
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Summary:Multiple myeloma (MM) is the second most common hematologic malignancy, characterized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often through an intermediate phase known as “smoldering” MM (sMM). Interestingly, while many genomic alterations (translocation, deletions, mutations) are usually found at early stages, they are not sufficient (alone) to determine disease evolution. The latter, indeed, relies on significant “epigenetic” alterations of different normal cell populations within the bone marrow (BM) niche, including the “evasion” from immune-system control. Additionally, MM cells could “educate” the BM immune microenvironment (BM-IM) towards a pro-inflammatory and immunosuppressive phenotype, which ultimately leads to disease evolution, drug resistance, and patients’ worse outcome. Indeed, it is not a case that the most important drugs for the treatment of MM include immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide) and monoclonal antibodies (daratumumab, isatuximab, and elotuzumab). On these bases, in this review, we describe the most recent advances in the comprehension of the role of the different cells composing the BM-IM, and we discuss the potential molecular targets, which could represent new opportunities to improve current treatment strategies for MM patients.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13133213