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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MDPI AG
2020-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/3/555 |
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| author | Lorenzo Castagnoli Francesca De Santis Tatiana Volpari Claudio Vernieri Elda Tagliabue Massimo Di Di Nicola Serenella M Pupa |
| author_facet | Lorenzo Castagnoli Francesca De Santis Tatiana Volpari Claudio Vernieri Elda Tagliabue Massimo Di Di Nicola Serenella M Pupa |
| author_sort | Lorenzo Castagnoli |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T07:08:31Z |
| format | Article |
| id | doaj.art-d3a7873f2366489f880c6bcf109da528 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:08:31Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d3a7873f2366489f880c6bcf109da5282023-09-02T23:18:15ZengMDPI AGCells2073-44092020-02-019355510.3390/cells9030555cells9030555Cancer Stem Cells: Devil or Savior—Looking behind the Scenes of Immunotherapy FailureLorenzo Castagnoli0Francesca De Santis1Tatiana Volpari2Claudio Vernieri3Elda Tagliabue4Massimo Di Di Nicola5Serenella M Pupa6Molecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Amadeo 42, 20133 Milan, ItalyUnit of Immunotherapy and Anticancer Innovative Therapeutics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian 1, 20133 Milan, ItalyUnit of Immunotherapy and Anticancer Innovative Therapeutics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian 1, 20133 Milan, ItalyDepartment of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, ItalyMolecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Amadeo 42, 20133 Milan, ItalyUnit of Immunotherapy and Anticancer Innovative Therapeutics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian 1, 20133 Milan, ItalyMolecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Amadeo 42, 20133 Milan, ItalyAlthough 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.https://www.mdpi.com/2073-4409/9/3/555cancer stem cellsimmunotherapytumor microenvironmentimmune checkpoint blockade |
| spellingShingle | Lorenzo Castagnoli Francesca De Santis Tatiana Volpari Claudio Vernieri Elda Tagliabue Massimo Di Di Nicola Serenella M Pupa Cancer Stem Cells: Devil or Savior—Looking behind the Scenes of Immunotherapy Failure Cells cancer stem cells immunotherapy tumor microenvironment immune checkpoint blockade |
| 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 | cancer stem cells immunotherapy tumor microenvironment immune checkpoint blockade |
| url | https://www.mdpi.com/2073-4409/9/3/555 |
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