Characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood, and daratumumab efficacy in vitro
Multiple myeloma is a haematological cancer characterised by the accumulation of clonal plasma cells in the bone marrow and is commonly treated with daratumumab, an anti-CD38 monoclonal antibody immunotherapy. Daratumumab often fails to induce stringent complete responses, due in part to resistance...
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Elsevier
2024-12-01
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| Series: | Brain, Behavior, & Immunity - Health |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354624001431 |
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| author | Harrison D. Collier-Bain Annabelle Emery Frankie F. Brown Adam J. Causer Rebecca Oliver Rachel Eddy Shoji Leach John Graby Daniel Augustine Sally Moore Josephine Crowe James Murray James E. Turner John P. Campbell |
| author_facet | Harrison D. Collier-Bain Annabelle Emery Frankie F. Brown Adam J. Causer Rebecca Oliver Rachel Eddy Shoji Leach John Graby Daniel Augustine Sally Moore Josephine Crowe James Murray James E. Turner John P. Campbell |
| author_sort | Harrison D. Collier-Bain |
| collection | DOAJ |
| description | Multiple myeloma is a haematological cancer characterised by the accumulation of clonal plasma cells in the bone marrow and is commonly treated with daratumumab, an anti-CD38 monoclonal antibody immunotherapy. Daratumumab often fails to induce stringent complete responses, due in part to resistance to antibody-dependent cellular cytotoxicity (ADCC) exerted by natural killer (NK)-cells and monocytes. Exercise bouts undertaken by healthy people induce lymphocytosis in blood, including to NK-cells and B-cells, but the effects of exercise are unknown in myeloma patients. In addition, whether exercise mobilises plasma cells has not been adequately investigated, and as such the potential impact of exercise on daratumumab treatment is unclear. In this exploratory pilot study, n = 16 smouldering multiple myeloma participants enrolled and n = 9 completed the study which comprised a bout of cycling 15% above anaerobic threshold for ∼30-min, with blood samples collected pre-, immediately post-, and 30-min post-exercise. Peripheral blood mononuclear cells were isolated from blood samples and incubated with the RPMI-8226 plasmacytoma cell line, with or without the presence of daratumumab to determine specific lysis using a calcein-release assay. Daratumumab-mediated cell lysis increased from 18.8% to 23.2% pre- to post-exercise, respectively (p < 0.001), owing to an increased frequency of CD3−CD56+CD16+ NK-cells (+348%), HLA-DR+CD14dimCD16+ monocytes (+125%), and HLA-DR+CD14+CD32+ monocytes (+41%) in blood (p < 0.01). However, overall, total plasma cells (CD38+CD138+) nor clonal plasma cells (CD38brightCD138+CD45−/dimCD19− with light-chain restriction) increased in blood (p > 0.05). Notably, we observed a 305% increase in NK-cells expressing CD38, the daratumumab target antigen, which might render NK-cells more susceptible to daratumumab-mediated fratricide – whereby NK-cells initiate ADCC against daratumumab-bound NK-cells. In conclusion, exercise modestly improved the efficacy of daratumumab-mediated ADCC in vitro. However, plasma cells were largely unchanged, and NK-cells expressing CD38 – the daratumumab target antigen – increased in blood. Future research should consider the optimal timings of exercise during daratumumab treatment in myeloma to avert exacerbation of daratumumab-mediated NK-cell lysis. |
| format | Article |
| id | doaj-art-6afa8708b3024e63913bbe863221bf42 |
| institution | Kabale University |
| issn | 2666-3546 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
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| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj-art-6afa8708b3024e63913bbe863221bf422024-12-02T05:06:38ZengElsevierBrain, Behavior, & Immunity - Health2666-35462024-12-0142100865Characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood, and daratumumab efficacy in vitroHarrison D. Collier-Bain0Annabelle Emery1Frankie F. Brown2Adam J. Causer3Rebecca Oliver4Rachel Eddy5Shoji Leach6John Graby7Daniel Augustine8Sally Moore9Josephine Crowe10James Murray11James E. Turner12John P. Campbell13Department for Health, University of Bath, United KingdomDepartment for Health, University of Bath, United KingdomDepartment for Health, University of Bath, United Kingdom; School of Applied Sciences, Edinburgh Napier University, Edinburgh, United KingdomDepartment for Health, University of Bath, United KingdomDepartment for Health, University of Bath, United Kingdom; Department of Haematology, Royal United Hospitals Bath NHS Foundation Trust, United KingdomDepartment for Health, University of Bath, United KingdomDepartment for Health, University of Bath, United KingdomDepartment for Health, University of Bath, United Kingdom; Department of Cardiology, Royal United Hospitals Bath NHS Foundation Trust, United KingdomDepartment of Haematology, Royal United Hospitals Bath NHS Foundation Trust, United KingdomDepartment of Haematology, Royal United Hospitals Bath NHS Foundation Trust, United KingdomDepartment of Haematology, Royal United Hospitals Bath NHS Foundation Trust, United KingdomDepartment of Haematology, Royal United Hospitals Bath NHS Foundation Trust, United KingdomDepartment for Health, University of Bath, United Kingdom; School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United KingdomDepartment for Health, University of Bath, United Kingdom; School of Medical and Health Sciences, Edith Cowan University, Perth, Australia; Corresponding author. Department for Health, University of Bath, BA2 7AY, United Kingdom.Multiple myeloma is a haematological cancer characterised by the accumulation of clonal plasma cells in the bone marrow and is commonly treated with daratumumab, an anti-CD38 monoclonal antibody immunotherapy. Daratumumab often fails to induce stringent complete responses, due in part to resistance to antibody-dependent cellular cytotoxicity (ADCC) exerted by natural killer (NK)-cells and monocytes. Exercise bouts undertaken by healthy people induce lymphocytosis in blood, including to NK-cells and B-cells, but the effects of exercise are unknown in myeloma patients. In addition, whether exercise mobilises plasma cells has not been adequately investigated, and as such the potential impact of exercise on daratumumab treatment is unclear. In this exploratory pilot study, n = 16 smouldering multiple myeloma participants enrolled and n = 9 completed the study which comprised a bout of cycling 15% above anaerobic threshold for ∼30-min, with blood samples collected pre-, immediately post-, and 30-min post-exercise. Peripheral blood mononuclear cells were isolated from blood samples and incubated with the RPMI-8226 plasmacytoma cell line, with or without the presence of daratumumab to determine specific lysis using a calcein-release assay. Daratumumab-mediated cell lysis increased from 18.8% to 23.2% pre- to post-exercise, respectively (p < 0.001), owing to an increased frequency of CD3−CD56+CD16+ NK-cells (+348%), HLA-DR+CD14dimCD16+ monocytes (+125%), and HLA-DR+CD14+CD32+ monocytes (+41%) in blood (p < 0.01). However, overall, total plasma cells (CD38+CD138+) nor clonal plasma cells (CD38brightCD138+CD45−/dimCD19− with light-chain restriction) increased in blood (p > 0.05). Notably, we observed a 305% increase in NK-cells expressing CD38, the daratumumab target antigen, which might render NK-cells more susceptible to daratumumab-mediated fratricide – whereby NK-cells initiate ADCC against daratumumab-bound NK-cells. In conclusion, exercise modestly improved the efficacy of daratumumab-mediated ADCC in vitro. However, plasma cells were largely unchanged, and NK-cells expressing CD38 – the daratumumab target antigen – increased in blood. Future research should consider the optimal timings of exercise during daratumumab treatment in myeloma to avert exacerbation of daratumumab-mediated NK-cell lysis.http://www.sciencedirect.com/science/article/pii/S2666354624001431Myeloma1Daratumumab2Exercise3ADCC4NK-cells5monocytes5 |
| spellingShingle | Harrison D. Collier-Bain Annabelle Emery Frankie F. Brown Adam J. Causer Rebecca Oliver Rachel Eddy Shoji Leach John Graby Daniel Augustine Sally Moore Josephine Crowe James Murray James E. Turner John P. Campbell Characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood, and daratumumab efficacy in vitro Brain, Behavior, & Immunity - Health Myeloma1 Daratumumab2 Exercise3 ADCC4 NK-cells5 monocytes5 |
| title | Characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood, and daratumumab efficacy in vitro |
| title_full | Characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood, and daratumumab efficacy in vitro |
| title_fullStr | Characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood, and daratumumab efficacy in vitro |
| title_full_unstemmed | Characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood, and daratumumab efficacy in vitro |
| title_short | Characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood, and daratumumab efficacy in vitro |
| title_sort | characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood and daratumumab efficacy in vitro |
| topic | Myeloma1 Daratumumab2 Exercise3 ADCC4 NK-cells5 monocytes5 |
| url | http://www.sciencedirect.com/science/article/pii/S2666354624001431 |
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