Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival
The immune checkpoint inhibitor ipilimumab provides long term survival in some metastatic melanoma patients, but the majority has no benefit, and may experience serious side effects. Here, we investigated the dynamics of plasma cytokine concentrations and their potential utility for predicting treat...
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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.2024.2440967 |
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| author | Ragnhild Reehorst Lereim Claire Dunn Elin Aamdal Sudhir Kumar Chauhan Oddbjørn Straume Tormod Kyrre Guren Jon Amund Kyte |
| author_facet | Ragnhild Reehorst Lereim Claire Dunn Elin Aamdal Sudhir Kumar Chauhan Oddbjørn Straume Tormod Kyrre Guren Jon Amund Kyte |
| author_sort | Ragnhild Reehorst Lereim |
| collection | DOAJ |
| description | The immune checkpoint inhibitor ipilimumab provides long term survival in some metastatic melanoma patients, but the majority has no benefit, and may experience serious side effects. Here, we investigated the dynamics of plasma cytokine concentrations and their potential utility for predicting treatment response, adverse events and overall survival (OS) in patients with metastatic melanoma undergoing ipilimumab monotherapy. A cohort of 148 patients was examined, with plasma samples collected prior to treatment initiation and at the end of the first and second treatment cycles. Concentrations of 48 plasma proteins were measured using a multiplex immunoassay. The results revealed a general increase in cytokine levels following the first ipilimumab dose, consistent with immune activation. Patients not responding to treatment exhibited significantly elevated baseline levels of G-CSF, IL-2RA, MIP-1a, and SCF, compared to tumor responders (p < 0.05). Furthermore, high levels of IL-2RA, IFNγ, PDGF-bb and MIG were linked to inferior OS, while high concentrations of MIF and RANTES were associated with improved OS (p < 0.05). A multivariate model containing CRP, LDH, ECOG, IL-2RA and PDGF-bb identified a subgroup of patients with poor OS. Patients who experienced severe immune-related adverse events within three months of treatment initiation had higher baseline concentrations of several cytokines, indicating a potential association between preexisting inflammation and adverse events. These findings indicate that the first dose of ipilimumab induces a systemic response with increased levels of circulating cytokines and suggest candidate biomarkers for clinical response, immune-mediated toxicity and survival. Further studies in independent patient cohorts are required to confirm the findings. |
| format | Article |
| id | doaj-art-93f0a7db4da542b0abd2f89bbfb4f1ac |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-93f0a7db4da542b0abd2f89bbfb4f1ac2025-08-20T01:58:36ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2024.2440967Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survivalRagnhild Reehorst Lereim0Claire Dunn1Elin Aamdal2Sudhir Kumar Chauhan3Oddbjørn Straume4Tormod Kyrre Guren5Jon Amund Kyte6Department of Cancer Immunology, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Immunology, Oslo University Hospital, Oslo, NorwayDepartment of Clinical Cancer Research, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Immunology, Oslo University Hospital, Oslo, NorwayDepartment of Oncology and Medical Physics, Haukeland University Hospital, Bergen, NorwayDepartment of Clinical Cancer Research, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Immunology, Oslo University Hospital, Oslo, NorwayThe immune checkpoint inhibitor ipilimumab provides long term survival in some metastatic melanoma patients, but the majority has no benefit, and may experience serious side effects. Here, we investigated the dynamics of plasma cytokine concentrations and their potential utility for predicting treatment response, adverse events and overall survival (OS) in patients with metastatic melanoma undergoing ipilimumab monotherapy. A cohort of 148 patients was examined, with plasma samples collected prior to treatment initiation and at the end of the first and second treatment cycles. Concentrations of 48 plasma proteins were measured using a multiplex immunoassay. The results revealed a general increase in cytokine levels following the first ipilimumab dose, consistent with immune activation. Patients not responding to treatment exhibited significantly elevated baseline levels of G-CSF, IL-2RA, MIP-1a, and SCF, compared to tumor responders (p < 0.05). Furthermore, high levels of IL-2RA, IFNγ, PDGF-bb and MIG were linked to inferior OS, while high concentrations of MIF and RANTES were associated with improved OS (p < 0.05). A multivariate model containing CRP, LDH, ECOG, IL-2RA and PDGF-bb identified a subgroup of patients with poor OS. Patients who experienced severe immune-related adverse events within three months of treatment initiation had higher baseline concentrations of several cytokines, indicating a potential association between preexisting inflammation and adverse events. These findings indicate that the first dose of ipilimumab induces a systemic response with increased levels of circulating cytokines and suggest candidate biomarkers for clinical response, immune-mediated toxicity and survival. Further studies in independent patient cohorts are required to confirm the findings.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2440967Biomarkeripilimumabmalignant melanomaplasma cytokines |
| spellingShingle | Ragnhild Reehorst Lereim Claire Dunn Elin Aamdal Sudhir Kumar Chauhan Oddbjørn Straume Tormod Kyrre Guren Jon Amund Kyte Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival OncoImmunology Biomarker ipilimumab malignant melanoma plasma cytokines |
| title | Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival |
| title_full | Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival |
| title_fullStr | Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival |
| title_full_unstemmed | Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival |
| title_short | Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival |
| title_sort | plasma protein dynamics during ipilimumab treatment in metastatic melanoma associations with tumor response adverse events and survival |
| topic | Biomarker ipilimumab malignant melanoma plasma cytokines |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2440967 |
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