Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial
Background Natural killer (NK) cells are one of the main effector populations of immunotherapy with monoclonal antibody and cytokines, used in combination with chemotherapy to treat children with high-risk neuroblastoma on this phase II trial. However, the impact of chemoimmunotherapy on NK cell kin...
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000176.full |
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| author | Rosa Nguyen David Cullins Barbara Rooney Natasha Sahr April Sykes Mary Beth McCarville Sara M Federico Amanda Sooter William E Janssen Gwendolyn Anthony Michael A Dyer Alberto S Pappo Wing H Leung Wayne L Furman |
| author_facet | Rosa Nguyen David Cullins Barbara Rooney Natasha Sahr April Sykes Mary Beth McCarville Sara M Federico Amanda Sooter William E Janssen Gwendolyn Anthony Michael A Dyer Alberto S Pappo Wing H Leung Wayne L Furman |
| author_sort | Rosa Nguyen |
| collection | DOAJ |
| description | Background Natural killer (NK) cells are one of the main effector populations of immunotherapy with monoclonal antibody and cytokines, used in combination with chemotherapy to treat children with high-risk neuroblastoma on this phase II trial. However, the impact of chemoimmunotherapy on NK cell kinetics, phenotype, and function is understudied.Methods We prospectively examined NK cell properties from 63 children with newly diagnosed neuroblastoma enrolled in a phase II trial (NCT01857934) and correlated our findings with tumor volume reduction after 2 courses of chemoimmunotherapy. NK cell studies were conducted longitudinally during chemoimmunotherapy and autologous hematopoietic cell transplantation (autoHCT) with optional haploidentical NK cell infusion and additional immunotherapy.Results Chemoimmunotherapy led to significant NK cytopenia, but complete NK cell recovery reliably occurred by day 21 of each therapy course as well as after autoHCT. Haploidentical NK cell infusion elevated the NK cell count transiently during autoHCT. NK cell cytotoxicity increased significantly during treatment compared with diagnosis. In addition, NK cells maintained their ability to respond to cytokine stimulation in culture longitudinally. Unsupervised cluster analysis of CD56bright NK cell count and tumor volume at diagnosis and after two courses of chemoimmunotherapy identified two patient groups with distinct primary tumor sizes and therapy responses.Conclusion After profound NK cytopenia due to chemoimmunotherapy, endogenously reconstituted NK cells exhibit enhanced NK cytotoxicity compared with pretherapy measurements. Our data suggest a relationship between CD56bright expression and tumor size before and after two courses of chemoimmunotherapy; however, future studies are necessary to confirm this relationship and its predictive significance.Trial registration number NCT01857934. |
| format | Article |
| id | doaj-art-61aa4de3291f4f04b11f55638ec3891c |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-61aa4de3291f4f04b11f55638ec3891c2025-08-20T02:49:52ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000176Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trialRosa Nguyen0David Cullins1Barbara Rooney2Natasha Sahr3April Sykes4Mary Beth McCarville5Sara M Federico6Amanda Sooter7William E Janssen8Gwendolyn Anthony9Michael A Dyer10Alberto S Pappo11Wing H Leung12Wayne L Furman131Department of Pediatrics, University of Maryland, USA5 Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA5 Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA3 Department of Biostatistics, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA3 Department of Biostatistics, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA4 Department of Radiological Sciences, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA1 Oncology Department, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA5 Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA5 Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA1 Oncology Department, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA6 Developmental Neurobiology, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA1 Oncology Department, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA5 Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children`s Research Hospital, Memphis, Tennessee, USA1 Oncology Department, St. Jude Children`s Research Hospital, Memphis, Tennessee, USABackground Natural killer (NK) cells are one of the main effector populations of immunotherapy with monoclonal antibody and cytokines, used in combination with chemotherapy to treat children with high-risk neuroblastoma on this phase II trial. However, the impact of chemoimmunotherapy on NK cell kinetics, phenotype, and function is understudied.Methods We prospectively examined NK cell properties from 63 children with newly diagnosed neuroblastoma enrolled in a phase II trial (NCT01857934) and correlated our findings with tumor volume reduction after 2 courses of chemoimmunotherapy. NK cell studies were conducted longitudinally during chemoimmunotherapy and autologous hematopoietic cell transplantation (autoHCT) with optional haploidentical NK cell infusion and additional immunotherapy.Results Chemoimmunotherapy led to significant NK cytopenia, but complete NK cell recovery reliably occurred by day 21 of each therapy course as well as after autoHCT. Haploidentical NK cell infusion elevated the NK cell count transiently during autoHCT. NK cell cytotoxicity increased significantly during treatment compared with diagnosis. In addition, NK cells maintained their ability to respond to cytokine stimulation in culture longitudinally. Unsupervised cluster analysis of CD56bright NK cell count and tumor volume at diagnosis and after two courses of chemoimmunotherapy identified two patient groups with distinct primary tumor sizes and therapy responses.Conclusion After profound NK cytopenia due to chemoimmunotherapy, endogenously reconstituted NK cells exhibit enhanced NK cytotoxicity compared with pretherapy measurements. Our data suggest a relationship between CD56bright expression and tumor size before and after two courses of chemoimmunotherapy; however, future studies are necessary to confirm this relationship and its predictive significance.Trial registration number NCT01857934.https://jitc.bmj.com/content/8/1/e000176.full |
| spellingShingle | Rosa Nguyen David Cullins Barbara Rooney Natasha Sahr April Sykes Mary Beth McCarville Sara M Federico Amanda Sooter William E Janssen Gwendolyn Anthony Michael A Dyer Alberto S Pappo Wing H Leung Wayne L Furman Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial Journal for ImmunoTherapy of Cancer |
| title | Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial |
| title_full | Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial |
| title_fullStr | Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial |
| title_full_unstemmed | Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial |
| title_short | Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial |
| title_sort | longitudinal nk cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase ii trial |
| url | https://jitc.bmj.com/content/8/1/e000176.full |
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