Serum interleukin-6 as a prognostic biomarker in patients with metastatic melanoma

Hoejberg, Lise; Bastholt, Lars; Johansen, Julia S.; Christensen, Ib Jarle; Gehl, Julie; Schmidt, Henrik

doi:10.1097/cmr.0b013e3283550aa5

Cited by 50 publications

(42 citation statements)

References 40 publications

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“…During treatment, the level of this cytokine increased significantly in a subset of patients introducing a widening of the range of concentration. IL6 has previously been linked to an adverse prognosis in malignant melanoma, 30,31 and in accordance with this, we found a non-significant reduced survival in patients with the highest IL6 levels by the 4th treatment. In order to determine whether the concentrations of this cytokine might just reflect a general unfavorable prognostic profile in patients with above median IL6 level, we scrutinized a possible correlation between the concentration of IL6 and LDH.…”

Section: Discussionsupporting

confidence: 75%

“…29 Numerous reports have focused on IL6 as a prognostic marker in metastatic melanoma and two relatively large studies have demonstrated a significant negative prognostic value of cytokine levels. 30,31 Other studies, however, have yielded conflicting results. 32 We measured serum-levels of IL6 at baseline, after the 1st and 3rd dose of Ipilimumab using a cytokine bead array.…”

Section: On-treatment Il6 Levels Correlate With Survivalmentioning

confidence: 86%

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Immunological correlates of treatment and response in stage IV malignant melanoma patients treated with Ipilimumab

et al. 2015

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Introduction: Ipilimumab is effective in the treatment of metastatic malignant melanoma, but few biomarkers reliably predict treatment response. Methods: Patients were treated with Ipilimumab for metastatic malignant melanoma. Blood and serum samples were collected before and during treatment. Mononuclear cells in peripheral blood were subjected to immune phenotypic analyses and cytokine levels were measured in serum samples. Results were correlated with clinical data. Results: A total of 40 patients were included in the analyses. Clinical response were associated with an increase after one series of treatment in absolute lymphocyte count (ALC) (p D 0.008), absolute T cell count (p D 0.02) and the absolute number of activated T cells in peripheral blood (p D 0.003). A high frequency of myeloid derived suppressor cells (MDSC) and a higher level of IL6 were associated with treatment failure, though not significantly. Levels of IL6 in serum above the median showed a tendency to associate with reduced survival by the 4th treatment series. Finally, treatment with Ipilimumab led to a decreased frequency of FOXP3C regulatory T cells (p D 0.009). Conclusion: Ipilimumab leads to increased ALC, T cell count and T cell activation in malignant melanoma patients responding to treatment. A high baseline frequency of myeloid-derived suppressor cells and high levels of IL6 is associated with a reduced chance of responding to therapy.

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Section: Discussionsupporting

confidence: 75%

Section: On-treatment Il6 Levels Correlate With Survivalmentioning

confidence: 86%

Immunological correlates of treatment and response in stage IV malignant melanoma patients treated with Ipilimumab

et al. 2015

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“…22, 23, 24 Increased serum levels of IL-6 were an independent prognostic biomarker of shorter overall survival in metastatic melanoma patients. 25 Therefore, the reduced miR-98 levels in these patients will likely result in a concomitant increase in IL-6 levels and poorer prognosis. Further studies will evaluate the correlation between IL-6 and miR-98 levels in melanoma patients as well as the prognostic value of determining miR-98 levels in these patients.…”

Section: Discussionmentioning

confidence: 99%

miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6

Qiao

et al. 2014

Exp Mol Med

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Dysregulated microRNA (miRNA) expression has a critical role in tumor development and metastasis. However, the mechanism by which miRNAs control melanoma metastasis is unknown. Here, we report reduced miR-98 expression in melanoma tissues with increasing tumor stage as well as metastasis; its expression is also negatively associated with melanoma patient survival. Furthermore, we demonstrate that miR-98 inhibits melanoma cell migration in vitro as well as metastatic tumor size in vivo. We also found that IL-6 is a target gene of miR-98, and IL-6 represses miR-98 levels via the Stat3-NF-κB-lin28B pathway. In an in vivo melanoma model, we demonstrate that miR-98 reduces melanoma metastasis and increases survival in part by reducing IL-6 levels; it also decreases Stat3 and p65 phosphorylation as well as lin28B mRNA levels. These results suggest that miR-98 inhibits melanoma metastasis in part through a novel miR-98-IL-6-negative feedback loop.

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“…Although patients with elevated pretreatment serum IL-6 have shorter overall survival compared with those with normal serum IL-6 [13], the results of IL-6 mRNA level in B16F1 tumors might be considered controversial. Ninjinto consists of ginseng, atractylodes lancea rhizome, ginger, and glycyrrhiza.…”

Section: Ninjinto Anti-tumor Effectmentioning

confidence: 95%

Anti‐tumor effect of Japanese herbal medicine Ninjinto in mouse melanoma: Efficacy of preventive treatment

Nakai

Kishida

Katoh

2015

Traditional & Kampo Medicine

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Aim:We evaluated the anti-tumor effect of the Japanese herbal medicine Ninjinto in a mouse melanoma. Methods: In in vitro experiments, B16F1 melanoma cells were cultured alone or in the presence of Ninjinto. Cell count, viability, concentration of interleukin (IL)-4 and 6, interferon (IFN)-γ in the medium, IL-6 messenger RNA level in cells, and morphological changes were assessed. In vivo, approximately 5 × 10 5 B16F1 cells in 50 μL phosphate-buffered saline were injected s.c. into the flank of C57BL/6 mice that had received plain drinking water or water containing 4 mg/mL of Ninjinto for 1 month. Tumor volume was measured using digital calipers. The presence of immune cells and expression of CD4, Foxp3, and IFN-γ at the site of the tumor were investigated on immunohistochemistry.

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Serum interleukin-6 as a prognostic biomarker in patients with metastatic melanoma

Cited by 50 publications

References 40 publications

Immunological correlates of treatment and response in stage IV malignant melanoma patients treated with Ipilimumab

Immunological correlates of treatment and response in stage IV malignant melanoma patients treated with Ipilimumab

miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6

Anti‐tumor effect of Japanese herbal medicine Ninjinto in mouse melanoma: Efficacy of preventive treatment

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