Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma
BackgroundPleural mesothelioma (PM) is a rare cancer with a dismal prognosis. Dual immune checkpoint inhibitors have improved overall survival, but the rate of immune-related adverse events (irAEs) is high. Serum cytokines reflect systemic immune reactions and may serve as biomarkers for irAEs.Patie...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1480183/full |
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| author | Saima Jamil Farooqi Saima Jamil Farooqi Zhi Zhao Åsa Kristina Öjlert Åsa Kristina Öjlert Solfrid Thunold Solfrid Thunold Hedvig Vidarsdotter Juul Maria Moksnes Bjaanæs Henrik Horndalsveen Henrik Horndalsveen Hanne Marte Gjertsen Nymoen Åslaug Helland Åslaug Helland Åslaug Helland Vilde Drageset Haakensen Vilde Drageset Haakensen Vilde Drageset Haakensen |
| author_facet | Saima Jamil Farooqi Saima Jamil Farooqi Zhi Zhao Åsa Kristina Öjlert Åsa Kristina Öjlert Solfrid Thunold Solfrid Thunold Hedvig Vidarsdotter Juul Maria Moksnes Bjaanæs Henrik Horndalsveen Henrik Horndalsveen Hanne Marte Gjertsen Nymoen Åslaug Helland Åslaug Helland Åslaug Helland Vilde Drageset Haakensen Vilde Drageset Haakensen Vilde Drageset Haakensen |
| author_sort | Saima Jamil Farooqi |
| collection | DOAJ |
| description | BackgroundPleural mesothelioma (PM) is a rare cancer with a dismal prognosis. Dual immune checkpoint inhibitors have improved overall survival, but the rate of immune-related adverse events (irAEs) is high. Serum cytokines reflect systemic immune reactions and may serve as biomarkers for irAEs.Patients and methodsPatients with pleural mesothelioma treated with nivolumab and ipilimumab with or without UV1 vaccine in the NIPU study were included. Serum cytokine levels were measured by Bio-Plex Pro Human Cytokine Screening 48-Plex Panel Assay. Correlations between cytokine levels and irAEs were analyzed by generalized linear mixed models to identify potential diagnostic and predictive biomarkers.ResultsHigher levels of MIG, eotaxin, MIP-1α, IP-10, TNF-α, MIP-1β, IL-4, MIF, IL-16, IL-2RA, SCGF.β and PDFG-BB at baseline are associated with increased risk of developing one or more irAEs. In particular, higher baseline levels of MIG are positively associated with thyroiditis and hypophysitis, and elevated levels of IP-10 and MIG to dermatitis. During the course of treatment, higher levels of MIG, eotaxin, MIF, TNF-α, MIP-1β, IL-4 and IL-16 are associated with an ongoing irAE. We found both predictive and diagnostic value of MIF with fatigue and of eotaxin with both colitis and pneumonitis. Higher levels of CTACK is associated with a lower risk of developing hepatitis, both before and after treatment.ConclusionsElevated levels of certain cytokines, both before and after onset of treatment, correlate with specific irAEs in PM patients receiving ICIs. These cytokines may be used as biomarkers to predict and detect irAES. |
| format | Article |
| id | doaj-art-afde90e2a30e4e34a31f707a41aeb105 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-afde90e2a30e4e34a31f707a41aeb1052025-08-20T02:50:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14801831480183Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesotheliomaSaima Jamil Farooqi0Saima Jamil Farooqi1Zhi Zhao2Åsa Kristina Öjlert3Åsa Kristina Öjlert4Solfrid Thunold5Solfrid Thunold6Hedvig Vidarsdotter Juul7Maria Moksnes Bjaanæs8Henrik Horndalsveen9Henrik Horndalsveen10Hanne Marte Gjertsen Nymoen11Åslaug Helland12Åslaug Helland13Åslaug Helland14Vilde Drageset Haakensen15Vilde Drageset Haakensen16Vilde Drageset Haakensen17Department of Oncology, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Genetics, Oslo University Hospital, Oslo, NorwayOslo Centre for Biostatistics and Epidemiology (OCBE), Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, NorwayDepartment of Oncology, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Genetics, Oslo University Hospital, Oslo, NorwayDepartment of Oncology, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Genetics, Oslo University Hospital, Oslo, NorwayCellular Therapy, Division of Cancer Medicine, Oslo University Hospital, Oslo, NorwayDepartment of Oncology, Oslo University Hospital, Oslo, NorwayDepartment of Oncology, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Genetics, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Genetics, Oslo University Hospital, Oslo, NorwayDepartment of Oncology, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Genetics, Oslo University Hospital, Oslo, NorwayUniversity of Oslo, Institute of Clinical Medicine, Oslo, NorwayDepartment of Oncology, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Genetics, Oslo University Hospital, Oslo, NorwayUniversity of Oslo, Institute of Clinical Medicine, Oslo, NorwayBackgroundPleural mesothelioma (PM) is a rare cancer with a dismal prognosis. Dual immune checkpoint inhibitors have improved overall survival, but the rate of immune-related adverse events (irAEs) is high. Serum cytokines reflect systemic immune reactions and may serve as biomarkers for irAEs.Patients and methodsPatients with pleural mesothelioma treated with nivolumab and ipilimumab with or without UV1 vaccine in the NIPU study were included. Serum cytokine levels were measured by Bio-Plex Pro Human Cytokine Screening 48-Plex Panel Assay. Correlations between cytokine levels and irAEs were analyzed by generalized linear mixed models to identify potential diagnostic and predictive biomarkers.ResultsHigher levels of MIG, eotaxin, MIP-1α, IP-10, TNF-α, MIP-1β, IL-4, MIF, IL-16, IL-2RA, SCGF.β and PDFG-BB at baseline are associated with increased risk of developing one or more irAEs. In particular, higher baseline levels of MIG are positively associated with thyroiditis and hypophysitis, and elevated levels of IP-10 and MIG to dermatitis. During the course of treatment, higher levels of MIG, eotaxin, MIF, TNF-α, MIP-1β, IL-4 and IL-16 are associated with an ongoing irAE. We found both predictive and diagnostic value of MIF with fatigue and of eotaxin with both colitis and pneumonitis. Higher levels of CTACK is associated with a lower risk of developing hepatitis, both before and after treatment.ConclusionsElevated levels of certain cytokines, both before and after onset of treatment, correlate with specific irAEs in PM patients receiving ICIs. These cytokines may be used as biomarkers to predict and detect irAES.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1480183/fullpleural mesotheliomaimmunotherapybiomarkerscytokinescheckpoint inhibition blockade |
| spellingShingle | Saima Jamil Farooqi Saima Jamil Farooqi Zhi Zhao Åsa Kristina Öjlert Åsa Kristina Öjlert Solfrid Thunold Solfrid Thunold Hedvig Vidarsdotter Juul Maria Moksnes Bjaanæs Henrik Horndalsveen Henrik Horndalsveen Hanne Marte Gjertsen Nymoen Åslaug Helland Åslaug Helland Åslaug Helland Vilde Drageset Haakensen Vilde Drageset Haakensen Vilde Drageset Haakensen Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma Frontiers in Immunology pleural mesothelioma immunotherapy biomarkers cytokines checkpoint inhibition blockade |
| title | Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma |
| title_full | Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma |
| title_fullStr | Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma |
| title_full_unstemmed | Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma |
| title_short | Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma |
| title_sort | serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma |
| topic | pleural mesothelioma immunotherapy biomarkers cytokines checkpoint inhibition blockade |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1480183/full |
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