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Immunotherapy with Antibodies in Multiple Myeloma: Monoclonals, Bispecifics, and Immunoconjugates
Review

Role and Modulation of NK Cells in Multiple Myeloma

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Service d’Hématologie, Hopital Brabois, CHRU Nancy, CNRS UMR 7563 IMoPa, Biopole de l’Université de Lorraine, 54500 Vandoeuvre-les-Nancy, France
2
Laboratoire HLA, Hopital Brabois, CHRU Nancy, CNRS UMR 7563 IMoPa, Biopole de l’Université de Lorraine, 54500 Vandoeuvre-les-Nancy, France
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Service d’Hématologie Clinique, Groupe Hospitalier Pitié-Salpêtrière APHP.6, Pavillon Georges Heuyer and INSERM CNRS 1135, NK and T Cell Immunity, Virus and Cancer, Centre d’Immunologie et des Pathologies Infectieuses (CIMI), Sorbonne Université, 47–83 Bd de l’Hôpital, CEDEX 13, 75651 Paris, France
*
Author to whom correspondence should be addressed.
Academic Editor: Nicolaus Kröger
Received: 5 March 2021 / Revised: 28 March 2021 / Accepted: 28 March 2021 / Published: 2 April 2021
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. View Full-Text
Keywords: myeloma; NK cells; immunomodulation; cell therapy; immunotherapy myeloma; NK cells; immunomodulation; cell therapy; immunotherapy
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MDPI and ACS Style

Rubio, M.T.; Dhuyser, A.; Nguyen, S. Role and Modulation of NK Cells in Multiple Myeloma. Hemato 2021, 2, 167-181. https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2020010

AMA Style

Rubio MT, Dhuyser A, Nguyen S. Role and Modulation of NK Cells in Multiple Myeloma. Hemato. 2021; 2(2):167-181. https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2020010

Chicago/Turabian Style

Rubio, Marie T., Adèle Dhuyser, and Stéphanie Nguyen. 2021. "Role and Modulation of NK Cells in Multiple Myeloma" Hemato 2, no. 2: 167-181. https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2020010

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