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Review
. 2021 Feb 5;13(4):625.
doi: 10.3390/cancers13040625.

The Immune Microenvironment in Multiple Myeloma: Friend or Foe?

Raquel Lopes  1   2 , Joana Caetano  1   3   4 , Bruna Ferreira  1   4 , Filipa Barahona  1   4 , Emilie Arnault Carneiro  1 , Cristina João  1   3   4
Affiliations
Review

The Immune Microenvironment in Multiple Myeloma: Friend or Foe?

Raquel Lopes et al. Cancers (Basel). .

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.

Keywords: cancer immunity; immunotherapy; multiple myeloma; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The 3E’s of immunoediting in the multiple myeloma (MM) bone marrow (BM) microenvironment. Immune cells can either eliminate cancer cells or facilitate escape from immune surveillance according to environmental cues. When neoplastic plasma cells start to arise, they can be recognized as strange and be eliminated by immune cells (Elimination Phase—“FOES”). However, cells can reach an equilibrium phase that involves a continuous eradication of myeloma cells. At the same time there is a Darwin selection of the most resistant clones and a decrease of immunogenic tumor cells. This stage is probably the longest phase and may occur over a period of several years, as it happens in monoclonal gammopathy of uncertain significance (MGUS) and low risk smoldering MM (SMM) patients. Afterwards, this novel population of myeloma clones that can model immunity, will grow and expand (Escape Phase—“FRIENDS”). pDC: plasmacytoid dendritic cell; mDC: myeloid dendritic cell, gd: gamma-delta T cells; Bregs: regulatory B cells; Tregs: regulatory T cells; M-MDSCs: monocytic myeloid-derived suppressor cells; PMN-MDSCs: polymorphonuclear MDSCs. Adapted from Dunn et al., 2004 [13].
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