Abstract

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 in an active form of myeloma. In fact, one of the hallmarks of MM is the development of a permissive BM milieu that provides a growth advantage to the malignant cells. Consequently, a better understanding of how myeloma cells interact with the BM niche compartments and disrupt the immune homeostasis is of utmost importance to develop more effective treatments. This review focuses on the most up-to-date knowledge regarding microenvironment-related mechanisms behind MM immune evasion and suppression, as well as promising molecules that are currently under pre-clinical tests targeting immune populations.

Highlights

  • Multiple myeloma (MM) is the second most frequent hematological cancer worldwide with a global incidence of 159,985 new cases in 2018 [1]

  • MM is an aggressive malignancy characterized by the clonal expansion of terminally differentiated B cells in the bone marrow (BM) and clinically defined by increased BM plasmacytosis, serum and/or urine monoclonal immunoglobulin, secretion of free light chains, hypercalcemia, renal insufficiency, anemia, and bone pain due to osteolytic disease [2,3]

  • In another study, Leone et al found that both myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) accumulate in the BM of patients during monoclonal gammopathy of uncertain significance (MGUS)-to-MM progression and these numbers correlate positively with the proportion of plasma cells in both MGUS and MM patients, indicating that Dendritic cells (DCs) accumulation is proportional to tumor burden

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Summary

Introduction

Multiple myeloma (MM) is the second most frequent hematological cancer worldwide with a global incidence of 159,985 new cases in 2018 [1]. MM is an aggressive malignancy characterized by the clonal expansion of terminally differentiated B cells in the bone marrow (BM) and clinically defined by increased BM plasmacytosis, serum and/or urine monoclonal immunoglobulin, secretion of free light chains, hypercalcemia, renal insufficiency, anemia, and bone pain due to osteolytic disease [2,3]. This disease is preceded by an asymptomatic premalignant condition termed monoclonal gammopathy of uncertain significance (MGUS), and in some patients, it is possible to distinguish an intermediate stage called smoldering MM (SMM) [4,5]. Notwithstanding, this review exclusively focuses on the current state of the art regarding the BM immune microenvironment

Myeloma Immune Microenvironment
Myeloid-Derived Suppressor Cells
Macrophages
Thecells
Dendritic Cells
T and NK Cells
Regulatory B Cells
Conclusions
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