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Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases

Despite multiple therapeutic approaches, the presence of liver metastases carries a guarded prognosis, urgently necessitating further clinical and scientific research to develop curative interventions. The liver is an immunoprivileged organ that suppresses the effectiveness of immunotherapies in pat...

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Autores principales: He, Kewen, Barsoumian, Hampartsoum B., Bertolet, Genevieve, Verma, Vivek, Leuschner, Carola, Koay, Eugene J., Ludmir, Ethan B., Hsu, Ethan, Pisipati, Esha, Voss, Tiffany A., Puebla-Osorio, Nahum, Cortez, Maria Angelica, Welsh, James W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714746/
https://www.ncbi.nlm.nih.gov/pubmed/34975924
http://dx.doi.org/10.3389/fimmu.2021.812210
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author He, Kewen
Barsoumian, Hampartsoum B.
Bertolet, Genevieve
Verma, Vivek
Leuschner, Carola
Koay, Eugene J.
Ludmir, Ethan B.
Hsu, Ethan
Pisipati, Esha
Voss, Tiffany A.
Puebla-Osorio, Nahum
Cortez, Maria Angelica
Welsh, James W.
author_facet He, Kewen
Barsoumian, Hampartsoum B.
Bertolet, Genevieve
Verma, Vivek
Leuschner, Carola
Koay, Eugene J.
Ludmir, Ethan B.
Hsu, Ethan
Pisipati, Esha
Voss, Tiffany A.
Puebla-Osorio, Nahum
Cortez, Maria Angelica
Welsh, James W.
author_sort He, Kewen
collection PubMed
description Despite multiple therapeutic approaches, the presence of liver metastases carries a guarded prognosis, urgently necessitating further clinical and scientific research to develop curative interventions. The liver is an immunoprivileged organ that suppresses the effectiveness of immunotherapies in patients with hepatic metastases. Cancer immunotherapies have been successfully bolstered by low-dose radiotherapy (LDRT), which is capable of reprogramming the tumor microenvironment (TME) from an immunosuppressive to an immunostimulatory one. Likewise, LDRT may be able to revoke the immune privilege enjoyed by the liver, permitting successful immunotherapies there. Here, we first review challenges that face the treatment of liver metastases. We next outline emerging preclinical and clinical evidence supporting enhanced systemic tumor control of LDRT in the context of cancer immunotherapy. Finally, we will discuss the rationale of combining liver-directed LDRT with immunostimulatory strategies to overcome immune resistance and achieve better clinical response. This notion is supported by a recent case study in which a patient who had progressed following T cell therapy experienced a complete response after LDRT to the liver.
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spelling pubmed-87147462021-12-30 Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases He, Kewen Barsoumian, Hampartsoum B. Bertolet, Genevieve Verma, Vivek Leuschner, Carola Koay, Eugene J. Ludmir, Ethan B. Hsu, Ethan Pisipati, Esha Voss, Tiffany A. Puebla-Osorio, Nahum Cortez, Maria Angelica Welsh, James W. Front Immunol Immunology Despite multiple therapeutic approaches, the presence of liver metastases carries a guarded prognosis, urgently necessitating further clinical and scientific research to develop curative interventions. The liver is an immunoprivileged organ that suppresses the effectiveness of immunotherapies in patients with hepatic metastases. Cancer immunotherapies have been successfully bolstered by low-dose radiotherapy (LDRT), which is capable of reprogramming the tumor microenvironment (TME) from an immunosuppressive to an immunostimulatory one. Likewise, LDRT may be able to revoke the immune privilege enjoyed by the liver, permitting successful immunotherapies there. Here, we first review challenges that face the treatment of liver metastases. We next outline emerging preclinical and clinical evidence supporting enhanced systemic tumor control of LDRT in the context of cancer immunotherapy. Finally, we will discuss the rationale of combining liver-directed LDRT with immunostimulatory strategies to overcome immune resistance and achieve better clinical response. This notion is supported by a recent case study in which a patient who had progressed following T cell therapy experienced a complete response after LDRT to the liver. Frontiers Media S.A. 2021-12-15 /pmc/articles/PMC8714746/ /pubmed/34975924 http://dx.doi.org/10.3389/fimmu.2021.812210 Text en Copyright © 2021 He, Barsoumian, Bertolet, Verma, Leuschner, Koay, Ludmir, Hsu, Pisipati, Voss, Puebla-Osorio, Cortez and Welsh https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
He, Kewen
Barsoumian, Hampartsoum B.
Bertolet, Genevieve
Verma, Vivek
Leuschner, Carola
Koay, Eugene J.
Ludmir, Ethan B.
Hsu, Ethan
Pisipati, Esha
Voss, Tiffany A.
Puebla-Osorio, Nahum
Cortez, Maria Angelica
Welsh, James W.
Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases
title Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases
title_full Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases
title_fullStr Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases
title_full_unstemmed Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases
title_short Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases
title_sort novel use of low-dose radiotherapy to modulate the tumor microenvironment of liver metastases
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714746/
https://www.ncbi.nlm.nih.gov/pubmed/34975924
http://dx.doi.org/10.3389/fimmu.2021.812210
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