Optimization of an orthotopic murine model of head and neck squamous cell carcinoma in fully immunocompetent mice – Role of toll-like-receptor 4 expressed on host cells

Vahle, Anne-Kristin; Kerem, Alexander; Öztürk, Ender; Bànkfalvi, Àgnes; Lang, Stephan; Brandau, Sven

doi:10.1016/j.canlet.2011.11.027

Cited by 27 publications

(29 citation statements)

References 21 publications

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“…To explore whether this phenomenon is limited to the subcutaneous (s.c.) injection site, we next extended our analysis to an orthotopic model recently developed by our group28. In this model, the tumour cells are injected into the floor of the mouth and the weight of the mice is recorded as a measure of tumour growth.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, effects of TLR2 and TLR4 activation by those endogenous DAMPs seem to be context-dependent as well. In a transplantable model of orthotopic head and neck cancer in C3H mice, the absence of TLR4 on host cells resulted in accelerated tumour growth28. In the context of chemo- or radiotherapy, the expression of TLR4 and activation of MyD88 mainly on dendritic cells were crucial for efficient induction of anti-tumour immunity20.…”

Section: Discussionmentioning

confidence: 99%

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Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth

et al. 2017

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Toll-like receptors (TLRs) are located either on the cell surface or intracellularly in endosomes and their activation normally contributes to the induction of protective immune responses. However, in cancer their activation by endogenous ligands can modulate tumour progression. It is currently unknown how endosomal TLRs regulate endogenous anti-tumour immunity. Here we show that TLR3, 7 and 9 deficiencies on host cells, after initial tumour growth, result in complete tumour regression and induction of anti-tumour immunity. Tumour regression requires the combined absence of all three receptors, is dependent on both CD4 and CD8 T cells and protects the mice from subsequent tumour challenge. While tumours in control mice are infiltrated by higher numbers of regulatory T cells, tumour regression in TLR-deficient mice is paralleled by altered vascular structure and strongly induced influx of cytotoxic and cytokine-producing effector T cells. Thus, endosomal TLRs may represent a molecular link between the inflamed tumour cell phenotype, anti-tumour immunity and the regulation of T-cell activation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth

et al. 2017

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“…TLR4 may also contribute to immune escape and chemoresistance [108]. TLR4 in host cells was involved in the regulation of tumor-related cachexia and tumor control [113]. Interestingly, a functional study showed defects in TLR4-mediated signaling in peripheral blood lymphocytes from oral cancer patients [114].…”

Section: Disturbance Of Signaling Pathways In Squamous Epithelial mentioning

confidence: 99%

Molecular mechanisms of ethanol-associated oro-esophageal squamous cell carcinoma

et al. 2015

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Alcohol drinking is a major etiological factor of oro-esophageal squamous cell carcinoma (OESCC). Both local and systemic effects of ethanol may promote carcinogenesis, especially among chronic alcoholics. However, molecular mechanisms of ethanol-associated OESCC are still not well understood. In this review, we summarize current understandings and propose three mechanisms of ethanol-associated OESCC: (1) Disturbance of systemic metabolism of nutrients: during ethanol metabolism in the liver, systemic metabolism of retinoids, zinc, iron and methyl groups is altered. These nutrients are known to be associated with the development of OESCC. (2) Disturbance of redox metabolism in squamous epithelial cells: when ethanol is metabolized in oro-esophageal squamous epithelial cells, reactive oxygen species are generated and produce oxidative damage. Meanwhile, ethanol may also disturb fatty-acid metabolism in these cells. (3) Disturbance of signaling pathways in squamous epithelial cells: due to its physico-chemical properties, ethanol changes cell membrane fluidity and shape, and may thus impact multiple signaling pathways. Advanced molecular techniques in genomics, epigenomics, metabolomics and microbiomics will help us elucidate how ethanol promotes OESCC.

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“…This procedure results in non-metastatic oral squamous cell carcinomas [27], the most common type of oral cancer in humans. This is a validated syngeneic model, permitting the use of mice with intact immune systems [28]. Body mass and tumor volume were measured twice/week.…”

Section: Methodsmentioning

confidence: 99%

Euflammation Attenuates Central and Peripheral Inflammation and Cognitive Consequences of an Immune Challenge after Tumor Development

Bever

Liu

Quan

et al. 2017

Neuroimmunomodulation

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Objective: Repeated subthreshold bacterial exposures in rodents cause novel euflammation that attenuates neuroinflammation and sickness behaviors upon subsequent infectious challenges to the host without eliciting illness behavior. The investigation of bacterial exposure effects on brain and behavior is clinically relevant because bacterial-based antitumor treatments are used successfully, but are suboptimal due to their illness side effects. In addition, behavioral consequences (depression, cognitive impairments) to homeostatic challenges that are associated with inflammation are prevalent and reduce the quality of life in cancer patients and survivors. Therefore, this study tested the potential for euflammation to attenuate behavioral consequences of an immune challenge in tumor-bearing mice. Methods: Mice with and without oral tumors in their flank underwent the established peripheral euflammatory protocol or vehicle treatment, followed by an acute peripheral immune challenge (lipopolysaccharide [LPS] injection) or PBS. Cognitive function and sickness behavior were assessed after the challenge, and peripheral and central inflammatory responses were measured. Results: Euflammation reduced LPS-induced peripheral and central inflammation in all mice; however, neuroinflammation was less attenuated in tumor-bearing mice compared with tumor-free controls. LPS-induced lethargy and cognitive impairments were more pronounced among tumor-bearing mice and were effectively attenuated with euflammation. Cognitive changes were independent of brain-derived growth factor gene expression in the hippocampus. Conclusion: These results suggest that induction of euflammation may be useful in alleviating the negative side effects of bacterial-based tumor treatments and in potentially attenuating common behavioral comorbidities associated with cancer or other chronic diseases.

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Optimization of an orthotopic murine model of head and neck squamous cell carcinoma in fully immunocompetent mice – Role of toll-like-receptor 4 expressed on host cells

Cited by 27 publications

References 21 publications

Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth

Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth

Molecular mechanisms of ethanol-associated oro-esophageal squamous cell carcinoma

Euflammation Attenuates Central and Peripheral Inflammation and Cognitive Consequences of an Immune Challenge after Tumor Development

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