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Novel Approaches to Improve the Efficacy of Immuno-Radiotherapy
Radiotherapy (RT) has been applied for decades as a treatment modality in the management of various types of cancer. Ionizing radiation induces tumor cell death, which in turn can either elicit protective anti-tumor immune responses or immunosuppression in the tumor micromilieu that contributes to l...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433964/ https://www.ncbi.nlm.nih.gov/pubmed/30941308 http://dx.doi.org/10.3389/fonc.2019.00156 |
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author | Shevtsov, Maxim Sato, Hiro Multhoff, Gabriele Shibata, Atsushi |
author_facet | Shevtsov, Maxim Sato, Hiro Multhoff, Gabriele Shibata, Atsushi |
author_sort | Shevtsov, Maxim |
collection | PubMed |
description | Radiotherapy (RT) has been applied for decades as a treatment modality in the management of various types of cancer. Ionizing radiation induces tumor cell death, which in turn can either elicit protective anti-tumor immune responses or immunosuppression in the tumor micromilieu that contributes to local tumor recurrence. Immunosuppression is frequently accompanied by the attraction of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), M2 tumor-associated macrophages (TAMs), T regulatory cells (Tregs), N2 neutrophils, and by the release of immunosuppressive cytokines (TGF-β, IL-10) and chemokines. Immune checkpoint pathways, particularly of the PD-1/PD-L1 axis, have been determined as key regulators of cancer immune escape. While IFN-dependent upregulation of PD-L1 has been extensively investigated, up-to-date studies indicated the importance of DNA damage signaling in the regulation of PD-L1 expression following RT. DNA damage dependent PD-L1 expression is upregulated by ATM/ATR/Chk1 kinase activities and cGAS/STING-dependent pathway, proving the role of DNA damage signaling in PD-L1 induced expression. Checkpoint blockade immunotherapies (i.e., application of anti-PD-1 and anti-PD-L1 antibodies) combined with RT were shown to significantly improve the objective response rates in therapy of various primary and metastatic malignancies. Further improvements in the therapeutic potential of RT are based on combinations of RT with other immunotherapeutic approaches including vaccines, cytokines and cytokine inducers, and an adoptive immune cell transfer (DCs, NK cells, T cells). In the current review we provide immunological rationale for a combination of RT with various immunotherapies as well as analysis of the emerging preclinical evidences for these therapies. |
format | Online Article Text |
id | pubmed-6433964 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64339642019-04-02 Novel Approaches to Improve the Efficacy of Immuno-Radiotherapy Shevtsov, Maxim Sato, Hiro Multhoff, Gabriele Shibata, Atsushi Front Oncol Oncology Radiotherapy (RT) has been applied for decades as a treatment modality in the management of various types of cancer. Ionizing radiation induces tumor cell death, which in turn can either elicit protective anti-tumor immune responses or immunosuppression in the tumor micromilieu that contributes to local tumor recurrence. Immunosuppression is frequently accompanied by the attraction of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), M2 tumor-associated macrophages (TAMs), T regulatory cells (Tregs), N2 neutrophils, and by the release of immunosuppressive cytokines (TGF-β, IL-10) and chemokines. Immune checkpoint pathways, particularly of the PD-1/PD-L1 axis, have been determined as key regulators of cancer immune escape. While IFN-dependent upregulation of PD-L1 has been extensively investigated, up-to-date studies indicated the importance of DNA damage signaling in the regulation of PD-L1 expression following RT. DNA damage dependent PD-L1 expression is upregulated by ATM/ATR/Chk1 kinase activities and cGAS/STING-dependent pathway, proving the role of DNA damage signaling in PD-L1 induced expression. Checkpoint blockade immunotherapies (i.e., application of anti-PD-1 and anti-PD-L1 antibodies) combined with RT were shown to significantly improve the objective response rates in therapy of various primary and metastatic malignancies. Further improvements in the therapeutic potential of RT are based on combinations of RT with other immunotherapeutic approaches including vaccines, cytokines and cytokine inducers, and an adoptive immune cell transfer (DCs, NK cells, T cells). In the current review we provide immunological rationale for a combination of RT with various immunotherapies as well as analysis of the emerging preclinical evidences for these therapies. Frontiers Media S.A. 2019-03-19 /pmc/articles/PMC6433964/ /pubmed/30941308 http://dx.doi.org/10.3389/fonc.2019.00156 Text en Copyright © 2019 Shevtsov, Sato, Multhoff and Shibata. http://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 | Oncology Shevtsov, Maxim Sato, Hiro Multhoff, Gabriele Shibata, Atsushi Novel Approaches to Improve the Efficacy of Immuno-Radiotherapy |
title | Novel Approaches to Improve the Efficacy of Immuno-Radiotherapy |
title_full | Novel Approaches to Improve the Efficacy of Immuno-Radiotherapy |
title_fullStr | Novel Approaches to Improve the Efficacy of Immuno-Radiotherapy |
title_full_unstemmed | Novel Approaches to Improve the Efficacy of Immuno-Radiotherapy |
title_short | Novel Approaches to Improve the Efficacy of Immuno-Radiotherapy |
title_sort | novel approaches to improve the efficacy of immuno-radiotherapy |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433964/ https://www.ncbi.nlm.nih.gov/pubmed/30941308 http://dx.doi.org/10.3389/fonc.2019.00156 |
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