Inflammatory markers in autoimmunity induced by checkpoint inhibitors
Copyright policy )Inflammatory markers in autoimmunity induced by checkpoint inhibitors
Abstract Purpose Immune checkpoint inhibitors (ICI) are highly effective in several cancer entities, but also invoke a variety of immune-related adverse events (irAE). These are mostly reversible, but can be life-threatening or even fatal. Currently, the pathogenesis is not fully understood, but crucial for effective treatment. Prediction and early detection of irAE could be facilitated and treatment optimized if relevant biomarkers and effector mechanisms were better characterized. Methods This study included a total of 45 irAE in patients with metastatic melanoma who were treated with ICI. All patients underwent a complete work-up with exclusion of other causes. Longitudinal blood samples were analyzed for a panel of soluble markers and compared to baseline and to patients who did not experience any irAE. Measurements included LDH, interleukin (IL)-6, IL-1β, IL-17, C-reactive protein (CRP) and tumor necrosis factor (TNF)-alpha as well as tumor markers S100 and melanoma inhibitory activity (MIA). Results During the early onset of irAE increases in serum IL-6 (from mean 24.4 pg/ml at baseline to 51.0 pg/ml; p = 0.003) and CRP (from mean 7.0 mg/l at baseline to 17.7 mg/l; p = 0.001) and a decrease in MIA (from mean 5.4 pg/ml at baseline to 4.8 pg/ml; p = 0.035) were detected. No changes in IL-17 were noted. These effects were observed for irAE of different organ systems. Conclusion Increases of a combination of IL-6 and CRP serum levels can be used for the early detection of irAE and tailored management. Interestingly, changes in MIA serum levels also correlate with irAE onset.
- University of Erlangen-Nuremberg Germany
- Comprehensive Cancer Center Erlangen Germany
- Universitätsklinikum Erlangen Germany
- Department of Dermatology Germany
Adult, Male, Uveal Neoplasms, Skin Neoplasms, Autoimmunity, Endocrine System Diseases, Cohort Studies, Immune checkpoint inhibitors, Melanoma, Cutaneous Malignant, Immune-related adverse events, Uveal Melanoma, Germany, DDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit, Biomarkers, Tumor, Humans, Neoplasm Metastasis, Immune Checkpoint Inhibitors, Melanoma, Inflammation, Inflammation/blood [MeSH] ; Gene Expression Regulation, Neoplastic/immunology [MeSH] ; Melanoma ; Inflammation/chemically induced [MeSH] ; Skin Neoplasms/blood [MeSH] ; Skin Neoplasms/drug therapy [MeSH] ; Cohort Studies [MeSH] ; Uveal Neoplasms/blood [MeSH] ; Autoimmunity/genetics [MeSH] ; Inflammation/genetics [MeSH] ; Male [MeSH] ; Immune Checkpoint Inhibitors/adverse effects [MeSH] ; Melanoma/pathology [MeSH] ; Case-Control Studies [MeSH] ; Autoimmunity/drug effects [MeSH] ; Uveal Neoplasms/pathology [MeSH] ; Diabetes Mellitus, Type 1/blood [MeSH] ; Melanoma/drug therapy [MeSH] ; Inflammation/immunology [MeSH] ; Female [MeSH] ; Original Article – Cancer Research ; Melanoma/genetics [MeSH] ; Adult [MeSH] ; Diabetes Mellitus, Type 1/chemically induced [MeSH] ; Humans [MeSH] ; Neoplasm Metastasis [MeSH] ; Uveal Neoplasms/drug therapy [MeSH] ; Melanoma/blood [MeSH] ; Uveal Neoplasms/genetics [MeSH] ; Skin Neoplasms/pathology [MeSH] ; Immune checkpoint inhibitors ; Immune Checkpoint Inhibitors/therapeutic use [MeSH] ; Cytokines ; Gene Expression Regulation, Neoplastic/drug effects [MeSH] ; Autoimmunity/immunology [MeSH] ; Skin Neoplasms/genetics [MeSH] ; Endocrine System Diseases/blood [MeSH] ; Biomarkers, Tumor/blood [MeSH] ; Biomarkers, Tumor/genetics [MeSH] ; Germany [MeSH] ; Endocrine System Diseases/immunology [MeSH] ; Diabetes Mellitus, Type 1/immunology [MeSH] ; Immune-related adverse events ; Endocrine System Diseases/chemically induced [MeSH] ; Immune Checkpoint Inhibitors/pharmacology [MeSH], Gene Expression Regulation, Neoplastic, Diabetes Mellitus, Type 1, Case-Control Studies, Cytokines, Female, Original Article – Cancer Research
Adult, Male, Uveal Neoplasms, Skin Neoplasms, Autoimmunity, Endocrine System Diseases, Cohort Studies, Immune checkpoint inhibitors, Melanoma, Cutaneous Malignant, Immune-related adverse events, Uveal Melanoma, Germany, DDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit, Biomarkers, Tumor, Humans, Neoplasm Metastasis, Immune Checkpoint Inhibitors, Melanoma, Inflammation, Inflammation/blood [MeSH] ; Gene Expression Regulation, Neoplastic/immunology [MeSH] ; Melanoma ; Inflammation/chemically induced [MeSH] ; Skin Neoplasms/blood [MeSH] ; Skin Neoplasms/drug therapy [MeSH] ; Cohort Studies [MeSH] ; Uveal Neoplasms/blood [MeSH] ; Autoimmunity/genetics [MeSH] ; Inflammation/genetics [MeSH] ; Male [MeSH] ; Immune Checkpoint Inhibitors/adverse effects [MeSH] ; Melanoma/pathology [MeSH] ; Case-Control Studies [MeSH] ; Autoimmunity/drug effects [MeSH] ; Uveal Neoplasms/pathology [MeSH] ; Diabetes Mellitus, Type 1/blood [MeSH] ; Melanoma/drug therapy [MeSH] ; Inflammation/immunology [MeSH] ; Female [MeSH] ; Original Article – Cancer Research ; Melanoma/genetics [MeSH] ; Adult [MeSH] ; Diabetes Mellitus, Type 1/chemically induced [MeSH] ; Humans [MeSH] ; Neoplasm Metastasis [MeSH] ; Uveal Neoplasms/drug therapy [MeSH] ; Melanoma/blood [MeSH] ; Uveal Neoplasms/genetics [MeSH] ; Skin Neoplasms/pathology [MeSH] ; Immune checkpoint inhibitors ; Immune Checkpoint Inhibitors/therapeutic use [MeSH] ; Cytokines ; Gene Expression Regulation, Neoplastic/drug effects [MeSH] ; Autoimmunity/immunology [MeSH] ; Skin Neoplasms/genetics [MeSH] ; Endocrine System Diseases/blood [MeSH] ; Biomarkers, Tumor/blood [MeSH] ; Biomarkers, Tumor/genetics [MeSH] ; Germany [MeSH] ; Endocrine System Diseases/immunology [MeSH] ; Diabetes Mellitus, Type 1/immunology [MeSH] ; Immune-related adverse events ; Endocrine System Diseases/chemically induced [MeSH] ; Immune Checkpoint Inhibitors/pharmacology [MeSH], Gene Expression Regulation, Neoplastic, Diabetes Mellitus, Type 1, Case-Control Studies, Cytokines, Female, Original Article – Cancer Research
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