Nucleic Acid Sensing Machinery: Targeting Innate Immune System for Cancer Therapy

Iurescia, Sandra; Fioretti, Daniela Piergili; Rinaldi, Monica

doi:10.2174/1574892812666171030163804

Cited by 25 publications

(21 citation statements)

References 92 publications

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“…As immune system antigens, exogenously purified circRNAs may mediate the activation of innate immunity by activating the retinoic acid-inducible gene I (RIG-I)-mediated pathway in vitro [65]. CircRNAinduced nucleic acid sensor RIG-I is a well-known innate immunity regulator [66,67], and RIG-I agonists have been shown to activate anticancer immune responses to fight tumours [68,69]. Therefore, exogenous circRNAs entering tumour cells have the potential to affect RIG-I and activate antitumour immunity (Fig.…”

Section: Circrnas Mediate Tumour Immune Surveillancementioning

confidence: 99%

Roles of circRNAs in the tumour microenvironment

et al. 2020

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The tumour microenvironment (TME) constitutes the area surrounding the tumour during its development and has been demonstrated to play roles in cancer-related diseases through crosstalk with tumour cells. Circular RNAs (circRNAs) are a subpopulation of endogenous noncoding RNAs (ncRNAs) that are ubiquitously expressed in eukaryotes and have multiple biological functions in the regulation of cancer onset and progression. An increasing number of studies have shown that circRNAs participate in the multifaceted biological regulation of the TME. However, details on the mechanisms involved have remained elusive until now. In this review, we analyse the effects of circRNAs on the TME from various perspectives, including immune surveillance, angiogenesis, hypoxia, matrix remodelling, exo-circRNAs and chemoradiation resistance. Currently, the enormous potential for circRNA use in targeted therapy and as noninvasive biomarkers have drawn our attention. We emphasize the prospect of targeting circRNAs as an essential strategy to regulate TME, overcome cancer resistance and improve therapeutic outcomes.

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Section: Circrnas Mediate Tumour Immune Surveillancementioning

confidence: 99%

Roles of circRNAs in the tumour microenvironment

et al. 2020

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“…Such immunogenicity leads to the production of type-I IFNs that were found to be crucial for both direct- and indirect-antigen presentation via distinct cell types (i.e. DCs and muscle cells, respectively), resulting in the adjuvant effect for the encoded antigen ( 91 , 92 ). However, the requirement for IFN-αβ in generating high-level antibody responses has yielded contradictory results.…”

Section: Stimulation Of Innate Immune Prrs By Dna Vaccinesmentioning

confidence: 99%

“…RIG-I and MDA5-activating DNA vaccines can elicit apoptotic and immunostimulatory effects and, thus, could induce growth inhibition or apoptosis of multiple types of cancer cells. Plasmid vector backbones expressing composite immunostimulatory RNAs that act as synergic RIG-I agonists lead to type-I IFNs production ( 92 , 94 ).…”

Section: Stimulation Of Innate Immune Prrs By Dna Vaccinesmentioning

confidence: 99%

Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies

2018

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The innate immune system provides the first line of defense against pathogen infection though also influences pathways involved in cancer immunosurveillance. The innate immune system relies on a limited set of germ line-encoded sensors termed pattern recognition receptors (PRRs), signaling proteins and immune response factors. Cytosolic receptors mediate recognition of danger damage-associated molecular patterns (DAMPs) signals. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Recent studies revealed that PRRs respond to nucleic acids (NA) released by dying, damaged, cancer cells, as danger DAMPs signals, and presence of signaling proteins across cancer types suggests that these signaling mechanisms may be involved in cancer biology. DAMPs play important roles in shaping adaptive immune responses through the activation of innate immune cells and immunological response to danger DAMPs signals is crucial for the host response to cancer and tumor rejection. Furthermore, PRRs mediate the response to NA in several vaccination strategies, including DNA immunization. As route of double-strand DNA intracellular entry, DNA immunization leads to expression of key components of cytosolic NA-sensing pathways. The involvement of NA-sensing mechanisms in the antitumor response makes these pathways attractive drug targets. Natural and synthetic agonists of NA-sensing pathways can trigger cell death in malignant cells, recruit immune cells, such as DCs, CD8+ T cells, and NK cells, into the tumor microenvironment and are being explored as promising adjuvants in cancer immunotherapies. In this minireview, we discuss how cGAS–STING and RIG-I–MAVS pathways have been targeted for cancer treatment in preclinical translational researches. In addition, we present a targeted selection of recent clinical trials employing agonists of cytosolic NA-sensing pathways showing how these pathways are currently being targeted for clinical application in oncology.

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“…Second, our data indicate that expression level and the inducible capability of functional RIG-I vary considerably in different NPC cells. Recent publications have highlighted therapeutic implications of RIG-I agonists as antitumor immunotherapy agents ( 33 ). Given RIG-I antiviral activity and ligands-mediated antitumor responses depend on functional RIG-I expression, this treatment should be a careful assessment especially for EBV-positive NPC, because RIG-I might contribute to NPC development ( 34 ) or RIG-I is destroyed by EBV and could not be induced by IFN-α as revealed in this study.…”

Section: Discussionmentioning

confidence: 99%

Latent Membrane Protein 1 of Epstein–Barr Virus Promotes RIG-I Degradation Mediated by Proteasome Pathway

Sun

Liu

et al. 2018

Front. Immunol.

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RIG-I signaling is critical to host innate immune response against RNA virus infection, and also can be activated against many kinds of cancer. Oncogene LMP1 of Epstein–Barr virus (EBV) contributes to various tumors progress. In this study, we have provided strong evidence that LMP1 inhibits Sendai virus mediated type I interferon production and downregulates RIG-I signaling pathway by promotion RIG-I degradation dependent on proteasome. Nineteen kinds of E3 ligase are identified by IP-MS as LMP1-interactors, they are candidate E3s, which are possibly recruited by LMP1 to mediate RIG-I degradation. CHIP is among these E3s, which has been reported to lead RIG-I degradation. Notably, we find C666-1, an EBV-positive nasopharyngeal carcinoma cell line, expresses low level of RIG-I, even treated with IFN-α, RIG-I expression could not be induced. This evidence indicates that EBV employs a unique strategy to evade RIG-I mediated immune responses.

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Nucleic Acid Sensing Machinery: Targeting Innate Immune System for Cancer Therapy

Cited by 25 publications

References 92 publications

Roles of circRNAs in the tumour microenvironment

Roles of circRNAs in the tumour microenvironment

Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies

Latent Membrane Protein 1 of Epstein–Barr Virus Promotes RIG-I Degradation Mediated by Proteasome Pathway

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