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Cancer Stem Cells: Devil or Savior—Looking behind the Scenes of Immunotherapy Failure

Although the introduction of immunotherapy has tremendously improved the prognosis of patients with metastatic cancers of different histological origins, some tumors fail to respond or develop resistance. Broadening the clinical efficacy of currently available immunotherapy strategies requires an im...

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Autores principales: Castagnoli, Lorenzo, De Santis, Francesca, Volpari, Tatiana, Vernieri, Claudio, Tagliabue, Elda, Di Nicola, Massimo, Pupa, Serenella M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140486/
https://www.ncbi.nlm.nih.gov/pubmed/32120774
http://dx.doi.org/10.3390/cells9030555
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author Castagnoli, Lorenzo
De Santis, Francesca
Volpari, Tatiana
Vernieri, Claudio
Tagliabue, Elda
Di Nicola, Massimo
Pupa, Serenella M.
author_facet Castagnoli, Lorenzo
De Santis, Francesca
Volpari, Tatiana
Vernieri, Claudio
Tagliabue, Elda
Di Nicola, Massimo
Pupa, Serenella M.
author_sort Castagnoli, Lorenzo
collection PubMed
description Although the introduction of immunotherapy has tremendously improved the prognosis of patients with metastatic cancers of different histological origins, some tumors fail to respond or develop resistance. Broadening the clinical efficacy of currently available immunotherapy strategies requires an improved understanding of the biological mechanisms underlying cancer immune escape. Globally, tumor cells evade immune attack using two main strategies: avoiding recognition by immune cells and instigating an immunosuppressive tumor microenvironment. Emerging data suggest that the clinical efficacy of chemotherapy or molecularly targeted therapy is related to the ability of these therapies to target cancer stem cells (CSCs). However, little is known about the role of CSCs in mediating tumor resistance to immunotherapy. Due to their immunomodulating features and plasticity, CSCs can be especially proficient at evading immune surveillance, thus potentially representing the most prominent malignant cell component implicated in primary or acquired resistance to immunotherapy. The identification of immunomodulatory properties of CSCs that include mechanisms that regulate their interactions with immune cells, such as bidirectional release of particular cytokines/chemokines, fusion of CSCs with fusogenic stromal cells, and cell-to-cell communication exerted by extracellular vesicles, may significantly improve the efficacy of current immunotherapy strategies. The purpose of this review is to discuss the current scientific evidence linking CSC biological, immunological, and epigenetic features to tumor resistance to immunotherapy.
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spelling pubmed-71404862020-04-13 Cancer Stem Cells: Devil or Savior—Looking behind the Scenes of Immunotherapy Failure Castagnoli, Lorenzo De Santis, Francesca Volpari, Tatiana Vernieri, Claudio Tagliabue, Elda Di Nicola, Massimo Pupa, Serenella M. Cells Review Although the introduction of immunotherapy has tremendously improved the prognosis of patients with metastatic cancers of different histological origins, some tumors fail to respond or develop resistance. Broadening the clinical efficacy of currently available immunotherapy strategies requires an improved understanding of the biological mechanisms underlying cancer immune escape. Globally, tumor cells evade immune attack using two main strategies: avoiding recognition by immune cells and instigating an immunosuppressive tumor microenvironment. Emerging data suggest that the clinical efficacy of chemotherapy or molecularly targeted therapy is related to the ability of these therapies to target cancer stem cells (CSCs). However, little is known about the role of CSCs in mediating tumor resistance to immunotherapy. Due to their immunomodulating features and plasticity, CSCs can be especially proficient at evading immune surveillance, thus potentially representing the most prominent malignant cell component implicated in primary or acquired resistance to immunotherapy. The identification of immunomodulatory properties of CSCs that include mechanisms that regulate their interactions with immune cells, such as bidirectional release of particular cytokines/chemokines, fusion of CSCs with fusogenic stromal cells, and cell-to-cell communication exerted by extracellular vesicles, may significantly improve the efficacy of current immunotherapy strategies. The purpose of this review is to discuss the current scientific evidence linking CSC biological, immunological, and epigenetic features to tumor resistance to immunotherapy. MDPI 2020-02-27 /pmc/articles/PMC7140486/ /pubmed/32120774 http://dx.doi.org/10.3390/cells9030555 Text en © 2020 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
Castagnoli, Lorenzo
De Santis, Francesca
Volpari, Tatiana
Vernieri, Claudio
Tagliabue, Elda
Di Nicola, Massimo
Pupa, Serenella M.
Cancer Stem Cells: Devil or Savior—Looking behind the Scenes of Immunotherapy Failure
title Cancer Stem Cells: Devil or Savior—Looking behind the Scenes of Immunotherapy Failure
title_full Cancer Stem Cells: Devil or Savior—Looking behind the Scenes of Immunotherapy Failure
title_fullStr Cancer Stem Cells: Devil or Savior—Looking behind the Scenes of Immunotherapy Failure
title_full_unstemmed Cancer Stem Cells: Devil or Savior—Looking behind the Scenes of Immunotherapy Failure
title_short Cancer Stem Cells: Devil or Savior—Looking behind the Scenes of Immunotherapy Failure
title_sort cancer stem cells: devil or savior—looking behind the scenes of immunotherapy failure
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140486/
https://www.ncbi.nlm.nih.gov/pubmed/32120774
http://dx.doi.org/10.3390/cells9030555
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