Low triglyceride levels are associated with increased risk of immune-related adverse events in patients receiving immune checkpoint inhibitors
Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy by enhancing anti-tumor immune responses, yet their use can lead to immune-related adverse events (irAE), including neurological complications. Despite their clinical relevance, predictive biomarkers for irAE remain scarce, and ea...
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2547271 |
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| author | Nora Möhn Emily Narten Laura Duzzi Janin Thomas Lea Grote-Levi Gernot Beutel Tabea Fröhlich Benjamin-Alexander Bollmann Thomas Wirth Imke von Wasielewski Ralf Gutzmer Florian Heidel Frank Pessler Walter Zobl Sven Schuchardt Philipp Ivanyi Sandra Nay Thomas Skripuletz |
| author_facet | Nora Möhn Emily Narten Laura Duzzi Janin Thomas Lea Grote-Levi Gernot Beutel Tabea Fröhlich Benjamin-Alexander Bollmann Thomas Wirth Imke von Wasielewski Ralf Gutzmer Florian Heidel Frank Pessler Walter Zobl Sven Schuchardt Philipp Ivanyi Sandra Nay Thomas Skripuletz |
| author_sort | Nora Möhn |
| collection | DOAJ |
| description | Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy by enhancing anti-tumor immune responses, yet their use can lead to immune-related adverse events (irAE), including neurological complications. Despite their clinical relevance, predictive biomarkers for irAE remain scarce, and early identification of at-risk patients is a major unmet need. In this prospective study, 200 patients undergoing ICI therapy were enrolled, of whom 59 underwent longitudinal metabolomic profiling at baseline, three months, and six months. Thirty-two patients who developed irAE were compared to 27 age- and sex-matched individuals without irAE. Multivariate analyses, including Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA), revealed distinct metabolomic signatures differentiating the two groups. Notably, baseline levels of triglyceride 20:0_34:1 were significantly lower in irAE(+) patients. In female patients, additional triglyceride species—20:1_34:2, 20:2_34:2, and 20:2_34:3—were also reduced prior to therapy and showed increases within three months of ICI initiation. These findings suggest that specific triglyceride species may serve as early biomarkers for irAE risk, particularly in female patients. The observed dynamic changes point to a potential link between lipid metabolism and immune-related toxicity, supporting the integration of metabolomic profiling into future strategies for risk stratification and personalized monitoring in cancer immunotherapy. |
| format | Article |
| id | doaj-art-37efcd94051441aa9cccf6f40e1c6ea2 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-37efcd94051441aa9cccf6f40e1c6ea22025-08-20T03:46:37ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2547271Low triglyceride levels are associated with increased risk of immune-related adverse events in patients receiving immune checkpoint inhibitorsNora Möhn0Emily Narten1Laura Duzzi2Janin Thomas3Lea Grote-Levi4Gernot Beutel5Tabea Fröhlich6Benjamin-Alexander Bollmann7Thomas Wirth8Imke von Wasielewski9Ralf Gutzmer10Florian Heidel11Frank Pessler12Walter Zobl13Sven Schuchardt14Philipp Ivanyi15Sandra Nay16Thomas Skripuletz17Department of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyDepartment of Pneumology, Hannover Medical School, Hannover, GermanyDepartment of Gastroenterology, Hannover Medical School, Hannover, GermanySkin-Cancer-Center, Hannover Medical School, Hannover, GermanySkin-Cancer-Center, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyResearch Group Biomarkers for Infectious Diseases, TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture of Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, GermanyResearch Group Biomarkers for Infectious Diseases, TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture of Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, GermanyDepartment of Bio- and Environmental Analytics, Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyImmune checkpoint inhibitors (ICI) have revolutionized cancer therapy by enhancing anti-tumor immune responses, yet their use can lead to immune-related adverse events (irAE), including neurological complications. Despite their clinical relevance, predictive biomarkers for irAE remain scarce, and early identification of at-risk patients is a major unmet need. In this prospective study, 200 patients undergoing ICI therapy were enrolled, of whom 59 underwent longitudinal metabolomic profiling at baseline, three months, and six months. Thirty-two patients who developed irAE were compared to 27 age- and sex-matched individuals without irAE. Multivariate analyses, including Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA), revealed distinct metabolomic signatures differentiating the two groups. Notably, baseline levels of triglyceride 20:0_34:1 were significantly lower in irAE(+) patients. In female patients, additional triglyceride species—20:1_34:2, 20:2_34:2, and 20:2_34:3—were also reduced prior to therapy and showed increases within three months of ICI initiation. These findings suggest that specific triglyceride species may serve as early biomarkers for irAE risk, particularly in female patients. The observed dynamic changes point to a potential link between lipid metabolism and immune-related toxicity, supporting the integration of metabolomic profiling into future strategies for risk stratification and personalized monitoring in cancer immunotherapy.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2547271Checkpoint inhibitorsimmune-related adverse eventsneurotoxicitybiomarkermetabolomics |
| spellingShingle | Nora Möhn Emily Narten Laura Duzzi Janin Thomas Lea Grote-Levi Gernot Beutel Tabea Fröhlich Benjamin-Alexander Bollmann Thomas Wirth Imke von Wasielewski Ralf Gutzmer Florian Heidel Frank Pessler Walter Zobl Sven Schuchardt Philipp Ivanyi Sandra Nay Thomas Skripuletz Low triglyceride levels are associated with increased risk of immune-related adverse events in patients receiving immune checkpoint inhibitors OncoImmunology Checkpoint inhibitors immune-related adverse events neurotoxicity biomarker metabolomics |
| title | Low triglyceride levels are associated with increased risk of immune-related adverse events in patients receiving immune checkpoint inhibitors |
| title_full | Low triglyceride levels are associated with increased risk of immune-related adverse events in patients receiving immune checkpoint inhibitors |
| title_fullStr | Low triglyceride levels are associated with increased risk of immune-related adverse events in patients receiving immune checkpoint inhibitors |
| title_full_unstemmed | Low triglyceride levels are associated with increased risk of immune-related adverse events in patients receiving immune checkpoint inhibitors |
| title_short | Low triglyceride levels are associated with increased risk of immune-related adverse events in patients receiving immune checkpoint inhibitors |
| title_sort | low triglyceride levels are associated with increased risk of immune related adverse events in patients receiving immune checkpoint inhibitors |
| topic | Checkpoint inhibitors immune-related adverse events neurotoxicity biomarker metabolomics |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2547271 |
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