Natural killer cell biology and therapy in multiple myeloma: challenges and opportunities
Abstract Despite therapeutic advancements, multiple myeloma (MM) remains incurable. NK cells have emerged as a promising option for the treatment of MM. NK cells are heterogenous and typically classified based on the relative expression of their surface markers (e.g., CD56 and CD16a). These cells el...
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| Format: | Article |
| Language: | English |
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BMC
2024-11-01
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| Series: | Experimental Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s40164-024-00578-4 |
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| author | Kamlesh Bisht Aimee Merino Rob Igarashi Laurent Gauthier Marielle Chiron Alexandre Desjonqueres Eric Smith Edward Briercheck Rizwan Romee Evren Alici Eric Vivier Michael O’Dwyer Helgi van de Velde |
| author_facet | Kamlesh Bisht Aimee Merino Rob Igarashi Laurent Gauthier Marielle Chiron Alexandre Desjonqueres Eric Smith Edward Briercheck Rizwan Romee Evren Alici Eric Vivier Michael O’Dwyer Helgi van de Velde |
| author_sort | Kamlesh Bisht |
| collection | DOAJ |
| description | Abstract Despite therapeutic advancements, multiple myeloma (MM) remains incurable. NK cells have emerged as a promising option for the treatment of MM. NK cells are heterogenous and typically classified based on the relative expression of their surface markers (e.g., CD56 and CD16a). These cells elicit an antitumor response in the presence of low mutational burden and without neoantigen presentation via germline-encoded activating and inhibitory receptors that identify the markers of transformation present on the MM cells. Higher NK cell activity is associated with improved survival and prognosis, whereas lower activity is associated with advanced clinical stage and disease progression in MM. Moreover, not all NK cell phenotypes contribute equally toward the anti-MM effect; higher proportions of certain NK cell phenotypes result in better outcomes. In MM, the proportion, phenotype, and function of NK cells are drastically varied between different disease stages; this is further influenced by the bone marrow microenvironment, proportion of activating and inhibitory receptors on NK cells, expression of homing receptors, and bone marrow hypoxia. Antimyeloma therapies, such as autologous stem cell transplant, immunomodulation, proteasome inhibition, and checkpoint inhibition, further modulate the NK cell landscape in the patients. Thus, NK cells can naturally work in tandem with anti-MM therapies and be strategically modulated for improved anti-MM effect. This review article describes immunotypic and phenotypic differences in NK cells along with the functional changes in homeostatic and malignant states and provides expert insights on strategies to harness the potential of NK cells for improving outcomes in MM. |
| format | Article |
| id | doaj-art-0b35578717bf4584af3e0678d86f8cc2 |
| institution | Kabale University |
| issn | 2162-3619 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj-art-0b35578717bf4584af3e0678d86f8cc22024-11-17T12:13:56ZengBMCExperimental Hematology & Oncology2162-36192024-11-0113111810.1186/s40164-024-00578-4Natural killer cell biology and therapy in multiple myeloma: challenges and opportunitiesKamlesh Bisht0Aimee Merino1Rob Igarashi2Laurent Gauthier3Marielle Chiron4Alexandre Desjonqueres5Eric Smith6Edward Briercheck7Rizwan Romee8Evren Alici9Eric Vivier10Michael O’Dwyer11Helgi van de Velde12Research and DevelopmentDivision of Hematology, Oncology, and Transplantation, University of MinnesotaResearch and DevelopmentInnate Pharma Research LaboratoriesResearch and DevelopmentResearch and DevelopmentDivision of Hematologic Malignancies and Transplantation, Dana Farber Cancer InstituteDivision of Hematologic Malignancies and Transplantation, Dana Farber Cancer InstituteDivision of Hematologic Malignancies and Transplantation, Dana Farber Cancer InstituteDepartment of Medicine, Karolinska Institutet (KI)Innate Pharma Research LaboratoriesDepartment of Haematology, University of GalwayResearch and DevelopmentAbstract Despite therapeutic advancements, multiple myeloma (MM) remains incurable. NK cells have emerged as a promising option for the treatment of MM. NK cells are heterogenous and typically classified based on the relative expression of their surface markers (e.g., CD56 and CD16a). These cells elicit an antitumor response in the presence of low mutational burden and without neoantigen presentation via germline-encoded activating and inhibitory receptors that identify the markers of transformation present on the MM cells. Higher NK cell activity is associated with improved survival and prognosis, whereas lower activity is associated with advanced clinical stage and disease progression in MM. Moreover, not all NK cell phenotypes contribute equally toward the anti-MM effect; higher proportions of certain NK cell phenotypes result in better outcomes. In MM, the proportion, phenotype, and function of NK cells are drastically varied between different disease stages; this is further influenced by the bone marrow microenvironment, proportion of activating and inhibitory receptors on NK cells, expression of homing receptors, and bone marrow hypoxia. Antimyeloma therapies, such as autologous stem cell transplant, immunomodulation, proteasome inhibition, and checkpoint inhibition, further modulate the NK cell landscape in the patients. Thus, NK cells can naturally work in tandem with anti-MM therapies and be strategically modulated for improved anti-MM effect. This review article describes immunotypic and phenotypic differences in NK cells along with the functional changes in homeostatic and malignant states and provides expert insights on strategies to harness the potential of NK cells for improving outcomes in MM.https://doi.org/10.1186/s40164-024-00578-4Multiple myelomaNatural killer cellsNatural killer cell activating receptorNatural killer cell inhibitory receptorImmunomodulationNatural killer cell engagers |
| spellingShingle | Kamlesh Bisht Aimee Merino Rob Igarashi Laurent Gauthier Marielle Chiron Alexandre Desjonqueres Eric Smith Edward Briercheck Rizwan Romee Evren Alici Eric Vivier Michael O’Dwyer Helgi van de Velde Natural killer cell biology and therapy in multiple myeloma: challenges and opportunities Experimental Hematology & Oncology Multiple myeloma Natural killer cells Natural killer cell activating receptor Natural killer cell inhibitory receptor Immunomodulation Natural killer cell engagers |
| title | Natural killer cell biology and therapy in multiple myeloma: challenges and opportunities |
| title_full | Natural killer cell biology and therapy in multiple myeloma: challenges and opportunities |
| title_fullStr | Natural killer cell biology and therapy in multiple myeloma: challenges and opportunities |
| title_full_unstemmed | Natural killer cell biology and therapy in multiple myeloma: challenges and opportunities |
| title_short | Natural killer cell biology and therapy in multiple myeloma: challenges and opportunities |
| title_sort | natural killer cell biology and therapy in multiple myeloma challenges and opportunities |
| topic | Multiple myeloma Natural killer cells Natural killer cell activating receptor Natural killer cell inhibitory receptor Immunomodulation Natural killer cell engagers |
| url | https://doi.org/10.1186/s40164-024-00578-4 |
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