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Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies
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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900005/ https://www.ncbi.nlm.nih.gov/pubmed/29686682 http://dx.doi.org/10.3389/fimmu.2018.00711 |
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author | Iurescia, Sandra Fioretti, Daniela Rinaldi, Monica |
author_facet | Iurescia, Sandra Fioretti, Daniela Rinaldi, Monica |
author_sort | Iurescia, Sandra |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5900005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59000052018-04-23 Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies Iurescia, Sandra Fioretti, Daniela Rinaldi, Monica Front Immunol Immunology 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. Frontiers Media S.A. 2018-04-09 /pmc/articles/PMC5900005/ /pubmed/29686682 http://dx.doi.org/10.3389/fimmu.2018.00711 Text en Copyright © 2018 Iurescia, Fioretti and Rinaldi. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Iurescia, Sandra Fioretti, Daniela Rinaldi, Monica Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies |
title | Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies |
title_full | Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies |
title_fullStr | Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies |
title_full_unstemmed | Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies |
title_short | Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies |
title_sort | targeting cytosolic nucleic acid-sensing pathways for cancer immunotherapies |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900005/ https://www.ncbi.nlm.nih.gov/pubmed/29686682 http://dx.doi.org/10.3389/fimmu.2018.00711 |
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