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Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues

SIMPLE SUMMARY: The incidence of biliary tract cancers (BTCs) is rising. Although therapeutic weapons are still limited, a better knowledge of the molecular landscape of these tumors has established the conditions for several phase I and II clinical trials in which molecular targeted drugs are combi...

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Autores principales: Schirizzi, Annalisa, De Leonardis, Giampiero, Lorusso, Vincenza, Donghia, Rossella, Rizzo, Alessandro, Vallarelli, Simona, Ostuni, Carmela, Troiani, Laura, Lolli, Ivan Roberto, Giannelli, Gianluigi, Ricci, Angela Dalia, D’Alessandro, Rosalba, Lotesoriere, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137233/
https://www.ncbi.nlm.nih.gov/pubmed/37190304
http://dx.doi.org/10.3390/cancers15082376
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author Schirizzi, Annalisa
De Leonardis, Giampiero
Lorusso, Vincenza
Donghia, Rossella
Rizzo, Alessandro
Vallarelli, Simona
Ostuni, Carmela
Troiani, Laura
Lolli, Ivan Roberto
Giannelli, Gianluigi
Ricci, Angela Dalia
D’Alessandro, Rosalba
Lotesoriere, Claudio
author_facet Schirizzi, Annalisa
De Leonardis, Giampiero
Lorusso, Vincenza
Donghia, Rossella
Rizzo, Alessandro
Vallarelli, Simona
Ostuni, Carmela
Troiani, Laura
Lolli, Ivan Roberto
Giannelli, Gianluigi
Ricci, Angela Dalia
D’Alessandro, Rosalba
Lotesoriere, Claudio
author_sort Schirizzi, Annalisa
collection PubMed
description SIMPLE SUMMARY: The incidence of biliary tract cancers (BTCs) is rising. Although therapeutic weapons are still limited, a better knowledge of the molecular landscape of these tumors has established the conditions for several phase I and II clinical trials in which molecular targeted drugs are combined with chemotherapy. Clinical research is investing great efforts in immunotherapy, which has recently transformed the treatment of many cancers. In BTCs, the efficacy of immunotherapy is limited by the high percentage of patients presenting immunosuppressive features in the tumor microenvironment. Angiogenesis is known to play a key role in modulating the microenvironment by excluding cytotoxic immune cells from the tumor bed, favoring an immunosuppressive activity. Therefore, blocking angiogenesis could create the conditions for more efficacious immunotherapy. This review considers clinical trials based on therapy combining angiogenesis and immune cell inhibitors, highlighting the clinical need for phase III studies in a precision-medicine era. ABSTRACT: Although biliary tract cancers are traditionally considered rare in Western countries, their incidence and mortality rates are rising worldwide. A better knowledge of the genomic landscape of these tumor types has broadened the number of molecular targeted therapies, including angiogenesis inhibitors. The role of immune checkpoint inhibitors (ICIs) could potentially change the first-line therapeutic approach, but monotherapy with ICIs has shown disappointing results in CCA. Several clinical trials are evaluating combination strategies that include immunotherapy together with other anticancer agents with a synergistic activity. The tumor microenvironment (TME) composition plays a pivotal role in the prognosis of BTC patients. The accumulation of immunosuppressive cell types, such as tumor-associated macrophages (TAMs) and regulatory T-cells, together with the poor infiltration of cytotoxic CD8+ T-cells, is known to predispose to a poor prognosis owing to the establishment of resistance mechanisms. Likewise, angiogenesis is recognized as a major player in modulating the TME in an immunosuppressive manner. This is the mechanistic rationale for combination treatment schemes blocking both immunity and angiogenesis. In this scenario, this review aims to provide an overview of the most recent completed or ongoing clinical trials combining immunotherapy and angiogenesis inhibitors with/without a chemotherapy backbone.
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spelling pubmed-101372332023-04-28 Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues Schirizzi, Annalisa De Leonardis, Giampiero Lorusso, Vincenza Donghia, Rossella Rizzo, Alessandro Vallarelli, Simona Ostuni, Carmela Troiani, Laura Lolli, Ivan Roberto Giannelli, Gianluigi Ricci, Angela Dalia D’Alessandro, Rosalba Lotesoriere, Claudio Cancers (Basel) Review SIMPLE SUMMARY: The incidence of biliary tract cancers (BTCs) is rising. Although therapeutic weapons are still limited, a better knowledge of the molecular landscape of these tumors has established the conditions for several phase I and II clinical trials in which molecular targeted drugs are combined with chemotherapy. Clinical research is investing great efforts in immunotherapy, which has recently transformed the treatment of many cancers. In BTCs, the efficacy of immunotherapy is limited by the high percentage of patients presenting immunosuppressive features in the tumor microenvironment. Angiogenesis is known to play a key role in modulating the microenvironment by excluding cytotoxic immune cells from the tumor bed, favoring an immunosuppressive activity. Therefore, blocking angiogenesis could create the conditions for more efficacious immunotherapy. This review considers clinical trials based on therapy combining angiogenesis and immune cell inhibitors, highlighting the clinical need for phase III studies in a precision-medicine era. ABSTRACT: Although biliary tract cancers are traditionally considered rare in Western countries, their incidence and mortality rates are rising worldwide. A better knowledge of the genomic landscape of these tumor types has broadened the number of molecular targeted therapies, including angiogenesis inhibitors. The role of immune checkpoint inhibitors (ICIs) could potentially change the first-line therapeutic approach, but monotherapy with ICIs has shown disappointing results in CCA. Several clinical trials are evaluating combination strategies that include immunotherapy together with other anticancer agents with a synergistic activity. The tumor microenvironment (TME) composition plays a pivotal role in the prognosis of BTC patients. The accumulation of immunosuppressive cell types, such as tumor-associated macrophages (TAMs) and regulatory T-cells, together with the poor infiltration of cytotoxic CD8+ T-cells, is known to predispose to a poor prognosis owing to the establishment of resistance mechanisms. Likewise, angiogenesis is recognized as a major player in modulating the TME in an immunosuppressive manner. This is the mechanistic rationale for combination treatment schemes blocking both immunity and angiogenesis. In this scenario, this review aims to provide an overview of the most recent completed or ongoing clinical trials combining immunotherapy and angiogenesis inhibitors with/without a chemotherapy backbone. MDPI 2023-04-19 /pmc/articles/PMC10137233/ /pubmed/37190304 http://dx.doi.org/10.3390/cancers15082376 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Schirizzi, Annalisa
De Leonardis, Giampiero
Lorusso, Vincenza
Donghia, Rossella
Rizzo, Alessandro
Vallarelli, Simona
Ostuni, Carmela
Troiani, Laura
Lolli, Ivan Roberto
Giannelli, Gianluigi
Ricci, Angela Dalia
D’Alessandro, Rosalba
Lotesoriere, Claudio
Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues
title Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues
title_full Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues
title_fullStr Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues
title_full_unstemmed Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues
title_short Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues
title_sort targeting angiogenesis in the era of biliary tract cancer immunotherapy: biological rationale, clinical implications, and future research avenues
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137233/
https://www.ncbi.nlm.nih.gov/pubmed/37190304
http://dx.doi.org/10.3390/cancers15082376
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