Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors
| Autor: | Martin R. Jakobsen, Anne Tranberg Madsen, Trine Heide Øllegaard, Boe Sandahl Sorensen, Jesper Geert Pedersen, Ninna Aggerholm-Pedersen, Kristine Raaby Gammelgaard |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Treatment response Immune checkpoint inhibitors Inflammation lcsh:RC254-282 Article Proinflammatory cytokine immune checkpoint inhibitors 03 medical and health sciences 0302 clinical medicine Internal medicine melanoma medicine neoplasms business.industry Melanoma Advanced stage biomarkers lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease cytokines 030104 developmental biology inflammation 030220 oncology & carcinogenesis Cohort Tumor necrosis factor alpha biological phenomena cell phenomena and immunity medicine.symptom business |
| Zdroj: | Cancers Cancers, Vol 12, Iss 1414, p 1414 (2020) Pedersen, J G, Madsen, A T, Gammelgaard, K R, Aggerholm-Pedersen, N, Sørensen, B S, Øllegaard, T H & Jakobsen, M R 2020, ' Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors ', Cancers, vol. 12, no. 6, 1414 . https://doi.org/10.3390/cancers12061414 Volume 12 Issue 6 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers12061414 |
| Popis: | Purpose: Checkpoint inhibitors have significantly improved treatment of metastatic melanoma. However, 40&ndash 60% of patients do not respond to therapy, emphasizing the need for better predictive biomarkers for treatment response to immune checkpoint inhibitors. Prorammed death-ligand 1(PD-L1) expression in tumor cells is currently used as a predictive biomarker however, it lacks specificity. Therefore, it is of utmost importance to identify other novel biomarkers that can predict treatment outcome. Experimental design: We studied a small cohort of 16 patients with advanced-stage melanoma treated with first-line checkpoint inhibitors. Plasma samples were collected prior to treatment initiation and continuously during the first year of treatment. Circulating tumor DNA (ctDNA) level and the expression of ten inflammatory cytokines were analyzed. Results: We found that the ctDNA-level in a blood sample collected after 6&ndash 8 weeks of therapy is predictive for response to checkpoint inhibitors. Patients with undetectable ctDNA had significantly longer progression-free survival (PFS) compared with patients with detectable ctDNA (median 26.3 vs. 2.1 months, p = 0.006). In parallel, we identified that high levels of the cytokines monocyte chemoattractant protein 1 (MCP1) and tumor necrosis factor a(TNFa) in baseline blood samples were significantly associated with longer PFS compared to low level of these cytokines (median not reached vs. 8.2 months p = 0.0008). Conclusions: These findings suggest that the levels of ctDNA, MCP1, and TNFa in baseline and early follow-up samples can predict disease progression in metastatic melanoma patients treated with checkpoint inhibitors. Potentially, these minimally invasive biomarkers may identify responders from non-responders. |
| Databáze: | OpenAIRE |
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