Interleukin‐6 predicts recurrence and survival among head and neck cancer patients

Duffy, Sonia A.; Taylor, Jeremy M. G.; Terrell, Jeffrey E.; Islam, Mohammad Mahmudul; Li, Yun; Fowler, Karen E.; Wolf, Gregory T.; Teknos, Theodoros N.

doi:10.1002/cncr.23615

Cited by 286 publications

(298 citation statements)

References 32 publications

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“…The important role of IL-6 was shown in clinical studies by Riedel et al (29) and Duffy et al (30), and discussed as a biomarker. The important role of IL-6 within the Stat3 signaling in tumor proliferation has also been shown.…”

Section: Discussionmentioning

confidence: 90%

IL-10 in the microenvironment of HNSCC inhibits the CpG ODN induced IFN-α secretion of pDCs

et al. 2018

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Abstract. It has been shown that head and neck squamous cell carcinoma (HNSCC) is infiltrated by plasmacytoid dendritic cells (pDCs). The HNSCC TH2 biased microenvironment leads to strong alterations of the cellular functions of pDC and thus impairs the initiation and function of adequate immune responses. In this work we comprehensively analyzed the capacity of CpG-oligonucleotides to activate interferon (IFN)-α secretion of human pDC in the presence of HNSCC. IFN-α secretion was measured using the ELISA Technique. Class A CpG dinucleotide 2216 was used in different concentrations and time frames to stimulate the IFN-α production of human pDC from peripheral blood in the absence and presence of the HNSCC microenvironment. To elucidate single components that might induce the reduction of IFN-α secretion, pDC were exposed to different concentrations of HNSCC relevant cytokines such as IL-6, IL-8 and IL-10. In accordance to former experiments we found that HNSCC micro milieu severely depresses up to 75% of IFN-α secretion capacity of pDCs, if the stimulating Class A CpG 2216 is added to the culture. Preincubation of HNSCC supernatant leads to unrestorable reduction of IFN-α secretion in pDC and can not be restored by CpG 2216. Incubation of pDCs with single cytokines relevant for cancer progression within the HNSCC micro milieu show that IL-6 or IL-8 have no influence on the IFN-α secretion in pDCs, whereas IL-10 massively impairs the secretion in a dose dependent manner. This effect can be potentiated by synergistic incubation with IL-6 and can be abrogated by blocking antibodies to the IL-10 receptor. Interestingly, incubation with IL-10 is not the only factor that impairs the IFN-α secretion, as incubation with the whole HNSCC supernatant is even more effective in reducing the secretion, implying that additional factors play a role. We conclude that restoration of HNSCC induced TH2 bias could be improved by the inhibition of immune cell cytokine receptors in addition to immunostimulating approaches with CpG motifs.

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Section: Discussionmentioning

confidence: 90%

IL-10 in the microenvironment of HNSCC inhibits the CpG ODN induced IFN-α secretion of pDCs

et al. 2018

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“…If cancer cells increasingly secrete IL-6, it may act in an autocrine manner to enhance the metastatic ability (17) and resistance of the tumor to treatment (18). The increased levels of IL-6 have been correlated with poor prognosis and survival rate in a variety of types of cancer (19)(20)(21)(22). Previous studies on solid tumors, including gastric, renal cell, colorectal, prostate, non-small cell lung, melanoma and head and neck cancer and hematologic malignancies, including myeloma and non-Hodgkin's lymphoma, have indicated the potential prognostic significance of IL-6 levels (19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Expression of interleukin-6 is associated with epithelial-mesenchymal transition and survival rates in gallbladder cancer

Zhang

Gong

Zhang

et al. 2014

Molecular Medicine Reports

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Abstract. The present study aimed to investigate the expression of interleukin-6 (IL-6) in gallbladder cancer (GBC) tissues and its correlation with survival rate. The association between IL-6 and epithelial-mesenchymal transition (EMT)-associated markers was also examined. Using immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, the protein and mRNA expression levels of IL-6, Twist, E-cadherin and Vimentin in 20 GBC tissues were analyzed. The IL-6, Twist and Vimentin proteins were overexpressed in 40, 20 and 70% of the human GBC samples, respectively. The protein expression of E-cadherin was higher in only 5% of the GBC samples. These differences were significant (P<0.05). Western blot analysis also revealed overexpression of IL-6, Twist and Vimentin and underexpression of E-cadherin in the GBC samples with poor differentiation, local invasion and a higher tumor-node-metastasis (TNM) stage (P<0.05). Higher mRNA expression levels of IL-6, Twist and Vimentin and a reduced expression level of E-cadherin were also demonstrated in the GBC tissues (P<0.05). The degree of differentiation, local invasion, lymph node metastasis and clinical stage were significantly associated with the mRNA expression levels of IL-6, Twist and E-cadherin. The increased expression levels of IL-6 and Twist and the reduced expression of E-cadherin correlated with shorter median survival rates (P<0.05). Line regression results revealed correlation among the mRNA expression levels of IL-6, Twist, E-cadherin and Vimentin. To the best of our knowledge, the present study is the first to demonstrate that IL-6 is associated with EMT-associated markers, tumor differentiation, local invasion, TNM stage and survival rates in GBC.

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“…This conclusion is supported independently by several clinical and laboratory observations. For example, high serum IL-6 levels are associated with worse prognosis for HNSCC patients, as well as with radioresistance (18,19). In addition, IL-6 secreted by oral SCCs can downregulate the costimulatory molecule, CD80, leading to a tolerogenic immune environment (20).…”

Section: Discussionmentioning

confidence: 99%

Cisplatin Treatment Induces a Transient Increase in Tumorigenic Potential Associated with High Interleukin-6 Expression in Head and Neck Squamous Cell Carcinoma

Poth

Guminski

Thomas

et al. 2010

Molecular Cancer Therapeutics

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Head and neck squamous cell carcinoma (HNSCC) is characterized by the 5-year survival rate of ∼50%. Despite aggressive surgical, radiation, and chemotherapeutic interventions, 30% to 40% of patients die from the development of recurrent or disseminated disease that is resistant to chemotherapy. As a model of recurrence, we examined the effects of cisplatin on the ability of head and neck cancer cells to initiate tumors in a xenotransplant model. HNSCC cells were treated in vitro with cisplatin at a concentration that elicited >99% cytotoxicity and assessed for tumorigenic potential in nonobese diabetic/severe combined immunodeficient mice. HNSCC cells that survived cisplatin treatment formed tumors in nonobese diabetic/severe combined immunodeficient mice more efficiently than nontreated cells. Cisplatin-resistant cells were characterized using clonal analysis, in vivo imaging, and transcriptomic profiling. Preliminary functional assessment of a gene, interleukin-6 (IL-6), highly upregulated in cisplatin-treated cells was carried out using clonogenicity and tumorigenicity assays. We show that cisplatin-induced IL-6 expression can contribute to the increase in tumorigenic potential of head and neck cancer cells but does not contribute to cisplatin resistance. Finally, through clonal analysis, we show that cisplatin-induced IL-6 expression and cisplatin-induced tumorigenicity are stochastically derived. We report that cisplatin treatment of head and neck cancer cells results in a transient accumulation of cisplatin-resistant, small, and IL-6-positive cells that are highly tumorigenic. These data also suggest that therapies that reduce IL-6 action may reduce recurrence rates and/or increase disease-free survival times in head and neck cancer patients, and thus, IL-6 represents a promising new target in HNSCC treatment. Mol Cancer Ther; 9(8); 2430-9. ©2010 AACR.

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Interleukin‐6 predicts recurrence and survival among head and neck cancer patients

Cited by 286 publications

References 32 publications

IL-10 in the microenvironment of HNSCC inhibits the CpG ODN induced IFN-α secretion of pDCs

IL-10 in the microenvironment of HNSCC inhibits the CpG ODN induced IFN-α secretion of pDCs

Expression of interleukin-6 is associated with epithelial-mesenchymal transition and survival rates in gallbladder cancer

Cisplatin Treatment Induces a Transient Increase in Tumorigenic Potential Associated with High Interleukin-6 Expression in Head and Neck Squamous Cell Carcinoma

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