Role and Modulation of NK Cells in Multiple Myeloma

Myeloma tumor cells are particularly dependent on their microenvironment and sensitive to cellular antitumor immune response, including natural killer (NK) cells. These later are essential innate lymphocytes implicated in the control of viral infections and cancers. Their cytotoxic activity is regul...

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Published inHemato Vol. 2; no. 2; pp. 167 - 181
Main Authors Rubio, Marie Thérèse, Dhuyser, Adèle, Nguyen, Stéphanie
Format Journal Article
LanguageEnglish
Published Aviano MDPI AG 01.06.2021
MDPI
Subjects
Antigens
Apoptosis
cell therapy
Cytokines
Cytotoxicity
Graft versus host disease
Hematology
Heparan sulfate
Human health and pathology
Immunoglobulins
Immunology
immunomodulation
Immunotherapy
Lectins
Leukemia
Life Sciences
Ligands
Multiple myeloma
myeloma
NK cells
Proteins
Stem cells
Transplants & implants
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Summary:Myeloma tumor cells are particularly dependent on their microenvironment and sensitive to cellular antitumor immune response, including natural killer (NK) cells. These later are essential innate lymphocytes implicated in the control of viral infections and cancers. Their cytotoxic activity is regulated by a balance between activating and inhibitory signals resulting from the complex interaction of surface receptors and their respective ligands. Myeloma disease evolution is associated with a progressive alteration of NK cell number, phenotype and cytotoxic functions. We review here the different therapeutic approaches that could restore or enhance NK cell functions in multiple myeloma. First, conventional treatments (immunomodulatory drugs-IMids and proteasome inhibitors) can enhance NK killing of tumor cells by modulating the expression of NK receptors and their corresponding ligands on NK and myeloma cells, respectively. Because of their ability to kill by antibody-dependent cell cytotoxicity, NK cells are important effectors involved in the efficacy of anti-myeloma monoclonal antibodies targeting the tumor antigens CD38, CS1 or BCMA. These complementary mechanisms support the more recent therapeutic combination of IMids or proteasome inhibitors to monoclonal antibodies. We finally discuss the ongoing development of new NK cell-based immunotherapies, such as ex vivo expanded killer cell immunoglobulin-like receptors (KIR)-mismatched NK cells, chimeric antigen receptors (CAR)-NK cells, check point and KIR inhibitors.
ISSN:2673-6357
2673-6357
DOI:10.3390/hemato2020010