Cargando…

Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response

Despite advances in cancer therapy, several persistent issues remain. These include cancer recurrence, effective targeting of aggressive or therapy-resistant cancers, and selective treatments for transformed cells. This review evaluates the current findings and highlights the potential of targeting...

Descripción completa

Detalles Bibliográficos
Autores principales: Ramirez, Manuel U., Hernandez, Salvador R., Soto-Pantoja, David R., Cook, Katherine L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981480/
https://www.ncbi.nlm.nih.gov/pubmed/31881743
http://dx.doi.org/10.3390/ijms21010169
_version_ 1783491090404343808
author Ramirez, Manuel U.
Hernandez, Salvador R.
Soto-Pantoja, David R.
Cook, Katherine L.
author_facet Ramirez, Manuel U.
Hernandez, Salvador R.
Soto-Pantoja, David R.
Cook, Katherine L.
author_sort Ramirez, Manuel U.
collection PubMed
description Despite advances in cancer therapy, several persistent issues remain. These include cancer recurrence, effective targeting of aggressive or therapy-resistant cancers, and selective treatments for transformed cells. This review evaluates the current findings and highlights the potential of targeting the unfolded protein response to treat cancer. The unfolded protein response, an evolutionarily conserved pathway in all eukaryotes, is initiated in response to misfolded proteins accumulating within the lumen of the endoplasmic reticulum. This pathway is initially cytoprotective, allowing cells to survive stressful events; however, prolonged activation of the unfolded protein response also activates apoptotic responses. This balance is key in successful mammalian immune response and inducing cell death in malignant cells. We discuss how the unfolded protein response affects cancer progression, survival, and immune response to cancer cells. The literature shows that targeting the unfolded protein response as a monotherapy or in combination with chemotherapy or immunotherapies increases the efficacy of these drugs; however, systemic unfolded protein response targeting may yield deleterious effects on immune cell function and should be taken into consideration. The material in this review shows the promise of both approaches, each of which merits further research.
format Online
Article
Text
id pubmed-6981480
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-69814802020-02-07 Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response Ramirez, Manuel U. Hernandez, Salvador R. Soto-Pantoja, David R. Cook, Katherine L. Int J Mol Sci Review Despite advances in cancer therapy, several persistent issues remain. These include cancer recurrence, effective targeting of aggressive or therapy-resistant cancers, and selective treatments for transformed cells. This review evaluates the current findings and highlights the potential of targeting the unfolded protein response to treat cancer. The unfolded protein response, an evolutionarily conserved pathway in all eukaryotes, is initiated in response to misfolded proteins accumulating within the lumen of the endoplasmic reticulum. This pathway is initially cytoprotective, allowing cells to survive stressful events; however, prolonged activation of the unfolded protein response also activates apoptotic responses. This balance is key in successful mammalian immune response and inducing cell death in malignant cells. We discuss how the unfolded protein response affects cancer progression, survival, and immune response to cancer cells. The literature shows that targeting the unfolded protein response as a monotherapy or in combination with chemotherapy or immunotherapies increases the efficacy of these drugs; however, systemic unfolded protein response targeting may yield deleterious effects on immune cell function and should be taken into consideration. The material in this review shows the promise of both approaches, each of which merits further research. MDPI 2019-12-25 /pmc/articles/PMC6981480/ /pubmed/31881743 http://dx.doi.org/10.3390/ijms21010169 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ramirez, Manuel U.
Hernandez, Salvador R.
Soto-Pantoja, David R.
Cook, Katherine L.
Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response
title Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response
title_full Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response
title_fullStr Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response
title_full_unstemmed Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response
title_short Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response
title_sort endoplasmic reticulum stress pathway, the unfolded protein response, modulates immune function in the tumor microenvironment to impact tumor progression and therapeutic response
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981480/
https://www.ncbi.nlm.nih.gov/pubmed/31881743
http://dx.doi.org/10.3390/ijms21010169
work_keys_str_mv AT ramirezmanuelu endoplasmicreticulumstresspathwaytheunfoldedproteinresponsemodulatesimmunefunctioninthetumormicroenvironmenttoimpacttumorprogressionandtherapeuticresponse
AT hernandezsalvadorr endoplasmicreticulumstresspathwaytheunfoldedproteinresponsemodulatesimmunefunctioninthetumormicroenvironmenttoimpacttumorprogressionandtherapeuticresponse
AT sotopantojadavidr endoplasmicreticulumstresspathwaytheunfoldedproteinresponsemodulatesimmunefunctioninthetumormicroenvironmenttoimpacttumorprogressionandtherapeuticresponse
AT cookkatherinel endoplasmicreticulumstresspathwaytheunfoldedproteinresponsemodulatesimmunefunctioninthetumormicroenvironmenttoimpacttumorprogressionandtherapeuticresponse