Natural Killer Cells in the Malignant Niche of Multiple Myeloma

Venglár, Ondrej; Bagó, Julio Rodriguez; Motais, Benjamin; Jelı́nek, Tomáš

doi:10.3389/fimmu.2021.816499

Cited by 16 publications

(11 citation statements)

References 313 publications

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“…32 Evidence suggests that changes to NK cell numbers and function also occur over the MM disease course. 149,150 The number of peripheral blood NK cells seems to decrease during the progression of monoclonal gammopathy of undetermined significance (MGUS) to early-stage untreated MM, 151 and to reduced numbers in advanced-stage untreated patients. 152 NK cells may also lose their cytotoxic capacity in advanced MM.…”

Section: Immune Microenvironment-related Resistance Mechanismsmentioning

confidence: 99%

Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma

Bisht,

Fukao,

Chiron

et al. 2023

Cancer Medicine

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BackgroundCD38 has been established as an important therapeutic target for multiple myeloma (MM), for which two CD38 antibodies are currently approved—daratumumab and isatuximab. CD38 is an ectoenzyme that degrades NAD and its precursors and is involved in the production of adenosine and other metabolites.AimAmong the various mechanisms by which CD38 antibodies can induce MM cell death is immunomodulation, including multiple pathways for CD38‐mediated T‐cell activation. Patients who respond to anti‐CD38 targeting treatment experience more marked changes in T‐cell expansion, activity, and clonality than nonresponders.ImplicationsResistance mechanisms that undermine the immunomodulatory effects of CD38‐targeting therapies can be tumor intrinsic, such as the downregulation of CD38 surface expression and expression of complement inhibitor proteins, and immune microenvironment‐related, such as changes to the natural killer (NK) cell numbers and function in the bone marrow niche. There are numerous strategies to overcome this resistance, which include identifying and targeting other therapeutic targets involved in, for example, adenosine production, the activation of NK cells or monocytes through immunomodulatory drugs and their combination with elotuzumab, or with bispecific T‐cell engagers.

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Section: Immune Microenvironment-related Resistance Mechanismsmentioning

confidence: 99%

Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma

Bisht,

Fukao,

Chiron

et al. 2023

Cancer Medicine

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“…Natural killer (NK) cells are a unique lymphocyte population able to exert cytotoxic activity without prior sensitization, highlighting their importance in innate anti‐tumour immunity. MM cells are known to express low levels of major histocompatibility class I on their surface, rendering them vulnerable to NK cell recognition and attack and subsequently highlighting the potential of NK surveillance in MM control 4 . Nevertheless, NK cells fail to acquire a functional cytotoxic phenotype amidst the highly immunosuppressive BM MM immune landscape and become increasingly exhausted as the disease develops.…”

Section: Figurementioning

confidence: 99%

Natural killer cells and bone marrow mesenchymal stem cells: A dangerous liaison in multiple myeloma

Botana

Moussay

Paggetti

2022

Clinical and Translational Dis

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BM-MSC, immune checkpoint blockade, NK cells, TIGITAccounting for 10% of all blood cancers, multiple myeloma (MM) is an incurable haematological malignancy characterized by the accumulation of clonal plasma cells in the bone marrow (BM) of patients. This malignancy often develops in elderly patients through the accumulation of a heterogeneous range of cytogenetic abnormalities that promote tumour growth and survival in the BM microenvironment. 1 The gold standard for the treatment of newly diagnosed patients without co-morbidities remains high-dose chemotherapy plus autologous stem cell transplantation. Unfortunately, MM patients relapse after each treatment regimen, leading to a continuous and dynamic search for new non-refractory therapeutic options. 2 Novel agents including immunomodulatory drugs, proteasome inhibitors, dexamethasone and more recently monoclonal antibodies have transformed the treatment paradigm of MM. Nowadays, these agents are extensively used in the clinic to target relapsed and refractory diseases. Of particular interest, immune checkpoint inhibitors have emerged as powerful tools to disrupt the deeply immunosuppressive interactions in the BM MM microenvironment,This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…Furthermore, NK cells are large granular lymphocytes that express CD16 and CD56 antigens and participate in nonspeci c immunity by directly acting on target cells or secreting antibodies to kill pathogenic microorganisms (17). Braquet et.al.…”

Section: Introductionmentioning

confidence: 99%

Circulating immune cells and multiple myeloma: A mendelian randomization study

Zhang,

Muhetaer,

Xiahou

et al. 2024

Preprint

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Objective Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Although plasma cells play an important role in this process, their relationship with other circulating immune cells has not been systematically investigated. Methods The single nucleotide polymorphism (SNP) data of 721 circulating immune cells and MM were obtained from GWAS summary data. After meeting the three assumptions of mendelian randomization (MR), we used inverse-variance weighted (IVW) as the main method to evaluate the causal association between the two. For positive results, we used multivariable mendelian randomization (MVMR) for adjustion and performed reverse MR analysis to assess the stability of the results. Results A total of 3 circulating immune cells are causally related to MM. Among them, Naive CD8 + T cell %T cell (IVW OR: 1.00123, 95%CI: 1.00015–1.00231, P value: 0.02518), Natural Killer T Absolute Count (IVW OR: 1.00062, 95%CI: 1.00006-1.00118, P value :0.03075) was a risk factor for MM, and CD28 + CD45RA + CD8 + T cell %T cell (IVW OR: 0.99993, 95%CI: 0.99987-1.00000, P value: 0.03549) was a protective factor for MM. This result remained stable in the MVMR analysis. Among them, Naive CD8 + T cell %T cell (IVW OR: 1.00200, 95%CI: 1.00058–1.00343, P value: 0.00586), Natural Killer T Absolute Count (IVW OR: 1.00051, 95%CI: 1.00002-1.00101, P value : 0.04225) was a risk factor for MM, and CD28 + CD45RA + CD8 + T cell %T cell (IVW OR: 0.99913, 95%CI: 0.99860–0.99967, P value: 0.00158) was a protective factor for MM. No reverse causal relationship was found between MM and these 3 circulating immune cells. Conclusions There was a causal association between 3 circulating immune cells and MM, which may provide a new strategy for the prevention and treatment of MM. Further randomized controlled studies are still needed to further elucidate their relationship.

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Natural Killer Cells in the Malignant Niche of Multiple Myeloma

Cited by 16 publications

References 313 publications

Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma

Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma

Natural killer cells and bone marrow mesenchymal stem cells: A dangerous liaison in multiple myeloma

Circulating immune cells and multiple myeloma: A mendelian randomization study

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