The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies
Immune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses...
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MDPI AG
2023-02-01
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Series: | International Journal of Molecular Sciences |
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Online Access: | https://www.mdpi.com/1422-0067/24/4/3226 |
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author | Ombretta Melaiu Gianluca Vanni Ilaria Portarena Chiara Adriana Pistolese Lucia Anemona Silvia Pomella Roberto Bei Oreste Claudio Buonomo Mario Roselli Alessandro Mauriello Giovanni Barillari |
author_facet | Ombretta Melaiu Gianluca Vanni Ilaria Portarena Chiara Adriana Pistolese Lucia Anemona Silvia Pomella Roberto Bei Oreste Claudio Buonomo Mario Roselli Alessandro Mauriello Giovanni Barillari |
author_sort | Ombretta Melaiu |
collection | DOAJ |
description | Immune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses in a greater proportion of BC patients. Recent studies have shown that the BC abnormal vasculature is associated with immune suppression in patients, and hampers both drug delivery and immune effector cell trafficking to tumor nests. Thus, strategies directed at normalizing (i.e., at remodeling and stabilizing) the immature, abnormal tumor vessels are receiving much attention. In particular, the combination of ICIs with tumor vessel normalizing agents is thought to hold great promise for the treatment of BC patients. Indeed, a compelling body of evidence indicates that the addition of low doses of antiangiogenic drugs to ICIs substantially improves antitumor immunity. In this review, we outline the impact that the reciprocal interactions occurring between tumor angiogenesis and immune cells have on the immune evasion and clinical progression of BC. In addition, we overview preclinical and clinical studies that are presently evaluating the therapeutic effectiveness of combining ICIs with antiangiogenic drugs in BC patients. |
first_indexed | 2024-03-11T08:44:02Z |
format | Article |
id | doaj.art-7387e27fbeb84922aef7b209c0686068 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-11T08:44:02Z |
publishDate | 2023-02-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
spelling | doaj.art-7387e27fbeb84922aef7b209c06860682023-11-16T20:57:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244322610.3390/ijms24043226The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical StudiesOmbretta Melaiu0Gianluca Vanni1Ilaria Portarena2Chiara Adriana Pistolese3Lucia Anemona4Silvia Pomella5Roberto Bei6Oreste Claudio Buonomo7Mario Roselli8Alessandro Mauriello9Giovanni Barillari10Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyBreast Unit, Department of Surgical Science, PTV Policlinico “Tor Vergata” University, Via Montpellier 1, 00133 Rome, ItalyMedical Oncology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyDepartment of Diagnostic and Molecular Imaging, Interventional Radiology and Radiotherapy, University Hospital of Rome “Tor Vergata”, Viale Oxford 81, 00133 Rome, ItalyAnatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyBreast Unit, Department of Surgical Science, PTV Policlinico “Tor Vergata” University, Via Montpellier 1, 00133 Rome, ItalyMedical Oncology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyAnatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyImmune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses in a greater proportion of BC patients. Recent studies have shown that the BC abnormal vasculature is associated with immune suppression in patients, and hampers both drug delivery and immune effector cell trafficking to tumor nests. Thus, strategies directed at normalizing (i.e., at remodeling and stabilizing) the immature, abnormal tumor vessels are receiving much attention. In particular, the combination of ICIs with tumor vessel normalizing agents is thought to hold great promise for the treatment of BC patients. Indeed, a compelling body of evidence indicates that the addition of low doses of antiangiogenic drugs to ICIs substantially improves antitumor immunity. In this review, we outline the impact that the reciprocal interactions occurring between tumor angiogenesis and immune cells have on the immune evasion and clinical progression of BC. In addition, we overview preclinical and clinical studies that are presently evaluating the therapeutic effectiveness of combining ICIs with antiangiogenic drugs in BC patients.https://www.mdpi.com/1422-0067/24/4/3226breast cancerangiogenesisvessel normalizationtumor microenvironmentimmunosuppressionantitumor immunity |
spellingShingle | Ombretta Melaiu Gianluca Vanni Ilaria Portarena Chiara Adriana Pistolese Lucia Anemona Silvia Pomella Roberto Bei Oreste Claudio Buonomo Mario Roselli Alessandro Mauriello Giovanni Barillari The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies International Journal of Molecular Sciences breast cancer angiogenesis vessel normalization tumor microenvironment immunosuppression antitumor immunity |
title | The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies |
title_full | The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies |
title_fullStr | The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies |
title_full_unstemmed | The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies |
title_short | The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies |
title_sort | combination of immune checkpoint blockade with tumor vessel normalization as a promising therapeutic strategy for breast cancer an overview of preclinical and clinical studies |
topic | breast cancer angiogenesis vessel normalization tumor microenvironment immunosuppression antitumor immunity |
url | https://www.mdpi.com/1422-0067/24/4/3226 |
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