Prognostic Value of Circulating Cytokines on Overall Survival and Disease-Free Survival in Cancer Patients

Visconti, Laura; Nelissen, Katherine; Deckx, Laura; Akker, Marjan van den; Adriaensen, Wim; Daniëls, Liesbeth; Matheï, Cathy; Linsen, Loes; Hellings, Niels; Stinissen, Piet; Buntinx, Frank

doi:10.2217/bmm.13.122

Cited by 22 publications

(15 citation statements)

References 81 publications

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“…Elevated circulating concentrations of IL-6 have been associated with poor prognosis in several cancers including DLBCL (39, 40). IL-6 receptor signals through STAT3 increase the transcription and production of IL-6, resulting in a feed forward autocrine loop (41).…”

Section: Resultsmentioning

confidence: 99%

AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer

et al. 2015

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Next-generation sequencing technologies have greatly expanded our understanding of cancer genetics. Antisense technology is an attractive platform with the potential to translate these advances into improved cancer therapeutics, because antisense oligonucleotide (ASO) inhibitors can be designed on the basis of gene sequence information alone. Recent human clinical data have demonstrated the potent activity of systemically administered ASOs targeted to genes expressed in the liver. Here, we describe the preclinical activity and initial clinical evaluation of a class of ASOs containing constrained ethyl modifications for targeting the gene encoding the transcription factor STAT3, a notoriously difficult protein to inhibit therapeutically. Systemic delivery of the unformulated ASO, AZD9150, decreased STAT3 expression in a broad range of preclinical cancer models and showed antitumor activity in lymphoma and lung cancer models. AZD9150 preclinical activity translated into single-agent antitumor activity in patients with highly treatment-refractory lymphoma and non-small cell lung cancer in a phase I dose escalation study.

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Section: Resultsmentioning

confidence: 99%

AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer

et al. 2015

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“…Guida and colleagues (46) have reported that IL8 was unrelated with prognoses in patients with metastatic melanoma, even though the group with the highest levels of IL8 presented the lowest median OS. Other groups have reported lack of association of IL8 and prognosis (34,(47)(48)(49). Complexity of IL8 functions, technical issues, and/or characteristics of the selected patient populations may explain such discrepancies.…”

Section: Discussionmentioning

confidence: 99%

Serum Interleukin-8 Reflects Tumor Burden and Treatment Response across Malignancies of Multiple Tissue Origins

Sanmamed

Carranza-Rua

Alfaro

et al. 2014

Clinical Cancer Research

210

158

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Purpose: Interleukin-8 (IL8) is a chemokine produced by malignant cells of multiple cancer types. It exerts various functions in shaping protumoral vascularization and inflammation/immunity. We evaluated sequential levels of serum IL8 in preclinical tumor models and in patients to assess its ability to estimate tumor burden.Experimental Design: IL8 levels were monitored by sandwich ELISAs in cultured tumor cells supernatants, tumor-xenografted mice serum, and in samples from 126 patients with cancer. We correlated IL8 serum levels with baseline tumor burden and with treatment-induced changes in tumor burden, as well as with prognosis.Results: IL8 concentrations correlated with the number of IL8-producing tumor cells in culture. In xenografted neoplasms, IL8 serum levels rapidly dropped after surgical excision, indicating an accurate correlation with tumor burden. In patients with melanoma (n ¼ 16), renal cell carcinoma (RCC; n ¼ 23), non-small cell lung cancer (NSCLC; n ¼ 21), or hepatocellular carcinoma (HCC; n ¼ 30), serum IL8 concentrations correlated with tumor burden and stage, survival (melanoma, n ¼ 16; RCC, n ¼ 23; HCC, n ¼ 33), and objective responses to therapy, including those to BRAF inhibitors (melanoma, n ¼ 16) and immunomodulatory monoclonal antibodies (melanoma, n ¼ 8). IL8 concentrations in urine (n ¼ 18) were mainly elevated in tumors with direct contact with the urinary tract.Conclusions: IL8 levels correlate with tumor burden in preclinical models and in patients with cancer.

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“…IL-6 predicts mortality risk among various HIVuninfected populations (eg, patients with cancer [25] and healthy elderly individuals [12]). IL-6 concentrations increase with HIV infection [26], though the mechanism is unclear [27].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Biomarkers and Mortality Risk Among HIV-Suppressed Men: A Multisite Prospective Cohort Study

Wada¹,

Bream

Martı́nez-Maza

et al. 2016

Clin Infect Dis.

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Background. Human immunodeficiency virus (HIV)-induced inflammation and immune activation persist after initiation of combination antiretroviral therapy (cART) and HIV suppression and may contribute to mortality risks that exceed those in HIVuninfected populations, though associations are unclear.Methods. In the prospective Multicenter AIDS Cohort Study, comprising men who have sex with men from Baltimore, Chicago, Los Angeles, and Pittsburgh, concentrations of 24 biomarkers of inflammation and immune activation were measured in stored serum from HIV-positive men obtained after cART-induced HIV suppression between 1996 and 2009. The outcome was nonaccidental death, with follow-up until 2014. We used Cox proportional hazards models to test whether biomarker concentrations predict time from HIV suppression to death and adjusted for multiple tests. Exploratory factor analysis (EFA) was employed to identify groupings of biomarkers that predict mortality risk.Results. Of 670 men followed up from HIV suppression, 54 died by the end of 2013. After adjustment for age, CD4 + cell count, hepatitis B or C virus infection, and smoking, concentrations in the highest quartile of 4 biomarkers were significantly associated with mortality risk after controlling the false discovery rate at 5%: interleukin (IL) 6 (hazard ratio, 3.54; 95% confidence interval, 2.06-6.10), soluble IL 2Rα (3.29, 1.85-5.85), soluble CD14 (2.67, 1.55-4.61), and chemokine (CXC motif ) ligand 13 (CXCL13; 2.26; 1.29-3.95). EFA yielded 2 biomarker groupings that were independent predictors of mortality risk.Conclusions. Despite having undetectable HIV RNA levels during cART, men with higher concentrations of several biomarkers (particularly IL 6, soluble IL 2Rα, soluble CD14, and CXCL13) had higher hazards of long-term mortality. Correlations observed among biomarker concentrations may represent underlying inflammatory processes that contribute to mortality risk.

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Prognostic Value of Circulating Cytokines on Overall Survival and Disease-Free Survival in Cancer Patients

Cited by 22 publications

References 81 publications

AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer

AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer

Serum Interleukin-8 Reflects Tumor Burden and Treatment Response across Malignancies of Multiple Tissue Origins

Inflammatory Biomarkers and Mortality Risk Among HIV-Suppressed Men: A Multisite Prospective Cohort Study

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