Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma
The treatment landscape for lymphoma and multiple myeloma, which disproportionally affect older adults, has been transformed by the advent of T cell-mediated immunotherapies, including immune checkpoint inhibition, T cell-engaging bispecific antibodies, and chimeric antigen receptor (CAR) T cell the...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-12-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/12/e009462.full |
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| author | Tamas Fulop Abdullah M Khan Valentín Ortiz-Maldonado Marcus Vetter Rainer Wirth Fabian Ullrich Paul J Bröckelmann Amin T Turki Elena-Diana Chiru Bastian von Tresckow Raul Cordoba Nina Rosa Neuendorff |
| author_facet | Tamas Fulop Abdullah M Khan Valentín Ortiz-Maldonado Marcus Vetter Rainer Wirth Fabian Ullrich Paul J Bröckelmann Amin T Turki Elena-Diana Chiru Bastian von Tresckow Raul Cordoba Nina Rosa Neuendorff |
| author_sort | Tamas Fulop |
| collection | DOAJ |
| description | The treatment landscape for lymphoma and multiple myeloma, which disproportionally affect older adults, has been transformed by the advent of T cell-mediated immunotherapies, including immune checkpoint inhibition, T cell-engaging bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, during the last decade. These treatment modalities re-enable the patient’s own immune system to combat malignant cells and offer the potential for sustained remissions and cure for various diseases.Age profoundly affects the physiological function of the immune system. The process of biological aging is largely driven by inflammatory signaling, which is reciprocally fueled by aging-related alterations of physiology and metabolism. In the T cell compartment, aging contributes to T cell senescence and exhaustion, increased abundance of terminally differentiated cells, a corresponding attrition in naïve T cell numbers, and a decrease in the breadth of the receptor repertoire. Furthermore, inflammatory signaling drives aging-related pathologies and contributes to frailty in older individuals. Thus, there is growing evidence of biological aging modulating the efficacy and toxicity of T cell-mediated immunotherapies.Here, we review the available evidence from biological and clinical studies focusing on the relationship between T cell-mediated treatment of hematologic malignancies and age. We discuss biological features potentially impacting clinical outcomes in various scenarios, and potential strategies to improve the safety and efficacy of immune checkpoint inhibitors, T cell-engaging bispecific antibodies, and CAR-T cell therapy in older patients. |
| format | Article |
| id | doaj-art-8afaf79800064ff3a516fd0cd7446516 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-8afaf79800064ff3a516fd0cd74465162025-08-20T02:38:18ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-12-01121210.1136/jitc-2024-009462Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphomaTamas Fulop0Abdullah M Khan1Valentín Ortiz-Maldonado2Marcus Vetter3Rainer Wirth4Fabian Ullrich5Paul J Bröckelmann6Amin T Turki7Elena-Diana Chiru8Bastian von Tresckow9Raul Cordoba10Nina Rosa Neuendorff1111 Department of Medicine, Division of Geriatrics, Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada6 Division of Hematology, The Ohio State University Comprehensive Cancer Center Arthur G James Cancer Hospital and Richard J Solove Research Institute, Columbus, Ohio, USA10 Department of Hematology, Oncoimmunotherapy Unit, Hospital Clínic de Barcelona, Barcelona, Spain7 Cancer Center Baselland, University of Basel Faculty of Medicine, Basel, Liestal, Switzerland8 Department of Geriatrics, Ruhr University Bochum, University Hospital Marien Hospital Herne, Herne, Germany1 Department of Hematology and Stem Cell Transplantation, West German Cancer Center and German Cancer Consortium (DKTK partner site Essen), University Duisburg-Essen, University Hospital Essen, Essen, Nordrhein-Westfalen, Germany2 Faculty of Medicine and University Hospital of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD) and German Hodgkin Study Group (GHSG), University of Cologne, Cologne, Germany4 Department of Hematology and Oncology, University Hospital Marien Hospital Herne, Herne, Nordrhein-Westfalen, Germany7 Cancer Center Baselland, University of Basel Faculty of Medicine, Basel, Liestal, Switzerland1 Department of Hematology and Stem Cell Transplantation, West German Cancer Center and German Cancer Consortium (DKTK partner site Essen), University Duisburg-Essen, University Hospital Essen, Essen, Nordrhein-Westfalen, Germany9 Department of Hematology, Lymphoma Unit, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain8 Department of Geriatrics, Ruhr University Bochum, University Hospital Marien Hospital Herne, Herne, GermanyThe treatment landscape for lymphoma and multiple myeloma, which disproportionally affect older adults, has been transformed by the advent of T cell-mediated immunotherapies, including immune checkpoint inhibition, T cell-engaging bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, during the last decade. These treatment modalities re-enable the patient’s own immune system to combat malignant cells and offer the potential for sustained remissions and cure for various diseases.Age profoundly affects the physiological function of the immune system. The process of biological aging is largely driven by inflammatory signaling, which is reciprocally fueled by aging-related alterations of physiology and metabolism. In the T cell compartment, aging contributes to T cell senescence and exhaustion, increased abundance of terminally differentiated cells, a corresponding attrition in naïve T cell numbers, and a decrease in the breadth of the receptor repertoire. Furthermore, inflammatory signaling drives aging-related pathologies and contributes to frailty in older individuals. Thus, there is growing evidence of biological aging modulating the efficacy and toxicity of T cell-mediated immunotherapies.Here, we review the available evidence from biological and clinical studies focusing on the relationship between T cell-mediated treatment of hematologic malignancies and age. We discuss biological features potentially impacting clinical outcomes in various scenarios, and potential strategies to improve the safety and efficacy of immune checkpoint inhibitors, T cell-engaging bispecific antibodies, and CAR-T cell therapy in older patients.https://jitc.bmj.com/content/12/12/e009462.full |
| spellingShingle | Tamas Fulop Abdullah M Khan Valentín Ortiz-Maldonado Marcus Vetter Rainer Wirth Fabian Ullrich Paul J Bröckelmann Amin T Turki Elena-Diana Chiru Bastian von Tresckow Raul Cordoba Nina Rosa Neuendorff Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma Journal for ImmunoTherapy of Cancer |
| title | Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma |
| title_full | Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma |
| title_fullStr | Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma |
| title_full_unstemmed | Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma |
| title_short | Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma |
| title_sort | impact of immunological aging on t cell mediated therapies in older adults with multiple myeloma and lymphoma |
| url | https://jitc.bmj.com/content/12/12/e009462.full |
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