Differential immunomodulatory activity of tumor cell death induced by cancer therapeutic toll-like receptor ligands

Klein, Johanna C.; Wild, Clarissa A.; Lang, Stephan; Brandau, Sven

doi:10.1007/s00262-016-1828-3

Cited by 12 publications

(10 citation statements)

References 39 publications

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“…This cell death may be anti-tumoural in two ways: First, as a direct consequence, the number of tumour cells is reduced. Second, via a process termed ‘immunogenic cell death', additional activation of anti-tumour immunity may occur910. However, some evidence suggests that this type of immunogenic cell death may rather be associated with the effects of TLR ligands on RIG-I-like helicases11, another class of pattern recognition receptors responsive to synthetic and pathogenic nucleic acids.…”

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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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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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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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“…In addition to U1, other RNAs that are released from damaged tissue could serve as endogenous ligands for TLR3 through their secondary structures [ 45 ]. Moreover, cancer therapeutic RNA compounds induce cell death in tumors and serve as TLR3 ligands [ 46 ]. Therefore, identification of specific alterations in noncoding RNA induced by cocaine exposure may help to determine the mechanism of TLR3 activation and downstream NF-κB signaling.…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 3 modulates the behavioral effects of cocaine in mice

Zhu

et al. 2018

J Neuroinflammation

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BackgroundThe nucleus accumbens in the midbrain dopamine limbic system plays a key role in cocaine addiction. Toll-like receptors (TLRs) are important pattern-recognition receptors (PPRs) in the innate immune system that are also involved in drug dependence; however, the detailed mechanism is largely unknown.MethodsThe present study was designed to investigate the potential role of TLR3 in cocaine addiction. Cocaine-induced conditioned place preference (CPP), locomotor activity, and self-administration were used to determine the effects of TLR3 in the rewarding properties of cocaine. Lentivirus-mediated re-expression of Tlr3 (LV-TLR3) was applied to determine if restoration of TLR3 expression in the NAc is sufficient to restore the cocaine effect in TLR3−/− mice. The protein levels of phospho-NF-κB p65, IKKβ, and p-IκBα both in the cytoplasm and nucleus of cocaine-induced CPP mice were detected by Western blot.ResultsWe showed that both TLR3 deficiency and intra-NAc injection of TLR3 inhibitors significantly attenuated cocaine-induced CPP, locomotor activity, and self-administration in mice. Importantly, the TLR3−/− mice that received intra-NAc injection of LV-TLR3 displayed significant increases in cocaine-induced CPP and locomotor activity. Finally, we found that TLR3 inhibitor reverted cocaine-induced upregulation of phospho-NF-κB p65, IKKβ, and p-IκBα.ConclusionsTaken together, our results describe that TLR3 modulates cocaine-induced behaviors and provide further evidence supporting a role for central pro-inflammatory immune signaling in drug reward. We propose that TLR3 blockade could be a novel approach to treat cocaine addiction.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1130-8) contains supplementary material, which is available to authorized users.

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“…For LRYM_T versus LRYM_N, DEGs were up-regulated mainly in protein digestion and absorption and cytokine-cytokine receptor interaction; and DEGs were down-regulated mainly in ECM-receptor interaction. CXCL1, CXCL3, and CXCL5 were up-regulated; CXCL1, CXCL3, and CXCL5 are known to contribute to the invasion and metastasis [17,18]. Collagen, THBS, and fibronectin are known to contribute to ECM-receptor interaction, which is down-regulated.…”

Section: Discussionmentioning

confidence: 99%

RNA-Sequence Analysis Reveals Differentially Expressed Genes (DEGs) in Patients Exhibiting Different Risks of Tumor Metastasis

Dong

Long

et al. 2017

Med Sci Monit

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BackgroundBreast cancer is one of the most common malignancies in women. In a previous study, we found that for two patients who had a high risk of lymphatic metastasis, lymphatic metastasis did not occur; whereas, for two patients who had a low risk of lymphatic metastasis, lymphatic metastasis did occur.Material/MethodsWe analyzed the differential gene expressions of these four patients by RNA-sequence. The data (HRNM_T versus HRNM_N, LRYM_T versus LRYM_N, and HRNM_T versus LRYM_T) was then processed using differentially expressed genes (DEGs) analysis, functional analysis for DEGs, and PPI network construct.ResultsFor HRNM_T versus HRNM_N, there were 224 DEGs. There were 504 DEGs for LRYM_T versus LRYM_N, and 88 DEGs for LRYM_T versus LRYM_N. For HRNM_T versus HRNM_N, DEGs were up-regulated mainly in the cell cycle, the IL-17 signaling pathway, and the progesterone-mediated oocyte maturation; DEGs were down-regulated mainly in the IL-17 signaling pathway. For LRYM_T versus LRYM_N, DEGs were up-regulated mainly in protein digestion and absorption, and cytokine-cytokine receptor interaction; DEGs were down-regulated mainly in ECM-receptor interaction. For HRNM_T versus LRYM_T, DEGs were up-regulated mainly in the PPAR signaling pathway; DEGs were downregulated mainly in the adipocytokine signaling pathway. The DEGs were screened to construct PPI networks.ConclusionsThe GO and KEGG functional enrichments of HRNM_T versus HRNM_N, and LRYM_T versus LRYM_N were consistent with earlier studies. For HRNM_T versus LRYM_T, DEGs were up-regulated mainly in PPAR signaling; DEGs were down-regulated mainly in the adipocytokine pathway.

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Differential immunomodulatory activity of tumor cell death induced by cancer therapeutic toll-like receptor ligands

Cited by 12 publications

References 39 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

Toll-like receptor 3 modulates the behavioral effects of cocaine in mice

RNA-Sequence Analysis Reveals Differentially Expressed Genes (DEGs) in Patients Exhibiting Different Risks of Tumor Metastasis

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