Immunological Prognostic Factors in Multiple Myeloma

Abstract

Multiple myeloma (MM) is a plasma cell neoplasm characterized by an abnormal proliferation of clonal, terminally differentiated B lymphocytes. Current approaches for the treatment of MM focus on developing new diagnostic techniques; however, the search for prognostic markers is also crucial. This enables the classification of patients into risk groups and, thus, the selection of the most optimal treatment method. Particular attention should be paid to the possible use of immune factors, as the immune system plays a key role in the formation and course of MM. In this review, we focus on characterizing the components of the immune system that are of prognostic value in MM patients, in order to facilitate the development of new diagnostic and therapeutic directions.

Natural Killer Cells in the Malignant Niche of Multiple Myeloma

“…Without a doubt, impaired IL−15R/IL−2R signaling and distorted NK cell maturation contributes to the disease progression. Levels of soluble IL-2R in serum and surface expression of IL-2R on malignant PCs or mononuclear cells are significantly increased in MM, which also correlates with the active state of the disease (178,179). Quite unexpectedly, defects related to the IL-21 axis affect NK cell lytic abilities but not the maturation, even though IL-21 promotes NK cell differentiation (180)(181)(182).…”

Treatment Strategy for Multiple Myeloma to Improve Immunological Environment and Maintain MRD Negativity

“…To cure MM, it is important to improve the immune environment and ensure persistent minimal residual disease (MRD) negativity [ 3 , 4 , 5 ]. Notably, the immune environment of myeloma patients is characterized by an attenuated immune effect on tumor cells, creating an environment suitable for the survival of myeloma cells [ 3 , 4 ].…”

“…To cure MM, it is important to improve the immune environment and ensure persistent minimal residual disease (MRD) negativity [ 3 , 4 , 5 ]. Notably, the immune environment of myeloma patients is characterized by an attenuated immune effect on tumor cells, creating an environment suitable for the survival of myeloma cells [ 3 , 4 ]. However, an improved immune environment leads to the long-term survival of patients with myeloma due to enhanced immunological potency against myeloma cells [ 6 ].…”

Pretreatment Serum Levels of IL-1 Receptor Antagonist and IL-4 Are Predictors of Overall Survival in Multiple Myeloma Patients Treated with Bortezomib

“…Immune cells and associated cytokines play a crucial role in the growth, progression, and dissemination of MM. While the roles of some cytokines, such as IL-6, TGF-β, and IL-1β, are well described in the MM biology, those of others remain unclear [ 10 , 11 , 12 , 13 ]. Previous reports indicated that bortezomib treatment is associated with significantly reduced serum levels of many cytokines and chemokines, including the interleukins IL-1α/β, IL-3, IL-4, IL-5, IL-6, IL-8, IL-12p40, IL-12p70, and IL-13, as well as IFN-γ, TNF-α, MIP-1α/β, GM-CSF, CXCL1, RANTES, VEGF, and Eotaxin [ 11 , 12 , 13 ].…”

“…While the roles of some cytokines, such as IL-6, TGF-β, and IL-1β, are well described in the MM biology, those of others remain unclear [ 10 , 11 , 12 , 13 ]. Previous reports indicated that bortezomib treatment is associated with significantly reduced serum levels of many cytokines and chemokines, including the interleukins IL-1α/β, IL-3, IL-4, IL-5, IL-6, IL-8, IL-12p40, IL-12p70, and IL-13, as well as IFN-γ, TNF-α, MIP-1α/β, GM-CSF, CXCL1, RANTES, VEGF, and Eotaxin [ 11 , 12 , 13 ]. Our previous study investigated circulating cytokine, growth factor, and chemokine levels and their association with selected clinical and laboratory disease characteristics [ 11 ].…”