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Comprehensive screening for drugs that modify radiation-induced immune responses

BACKGROUND: Combination therapy based on radiotherapy and immune checkpoint inhibitors (ICIs) was recently reported as effective for various cancers. The radiation-induced immune response (RIIR) is an essential feature in ICI-combined radiotherapy; however, the effects of drugs used concomitantly wi...

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Autores principales: Okumura, Masayuki, Du, Junyan, Kageyama, Shun-Ichiro, Yamashita, Riu, Hakozaki, Yumi, Motegi, Atsushi, Hojo, Hidehiro, Nakamura, Masaki, Hirano, Yasuhiro, Okuma, Yusuke, Okuma, Hitomi S., Tsuchihara, Katsuya, Akimoto, Tetsuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174493/
https://www.ncbi.nlm.nih.gov/pubmed/35184156
http://dx.doi.org/10.1038/s41416-021-01688-0
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author Okumura, Masayuki
Du, Junyan
Kageyama, Shun-Ichiro
Yamashita, Riu
Hakozaki, Yumi
Motegi, Atsushi
Hojo, Hidehiro
Nakamura, Masaki
Hirano, Yasuhiro
Okuma, Yusuke
Okuma, Hitomi S.
Tsuchihara, Katsuya
Akimoto, Tetsuo
author_facet Okumura, Masayuki
Du, Junyan
Kageyama, Shun-Ichiro
Yamashita, Riu
Hakozaki, Yumi
Motegi, Atsushi
Hojo, Hidehiro
Nakamura, Masaki
Hirano, Yasuhiro
Okuma, Yusuke
Okuma, Hitomi S.
Tsuchihara, Katsuya
Akimoto, Tetsuo
author_sort Okumura, Masayuki
collection PubMed
description BACKGROUND: Combination therapy based on radiotherapy and immune checkpoint inhibitors (ICIs) was recently reported as effective for various cancers. The radiation-induced immune response (RIIR) is an essential feature in ICI-combined radiotherapy; however, the effects of drugs used concomitantly with RIIR remain unclear. We screened for drugs that can modify RIIR to understand the mutual relationship between radiotherapy and combined drugs in ICI-combined radiotherapy. METHODS: We established a high-throughput system with reporter gene assays for evaluating RIIR, focusing on factors acting downstream of the STING-IRF pathway, which can stimulate cancer cells, T cells, and dendritic cells. We further quantified the effects of 2595 drugs, including those approved by the Food and Drug Administration, on RIIR in vitro. RESULTS: The reporter assay results correlated well with the expression of immune response proteins such as programmed death-ligand 1. This high-throughput system enabled the identification of drugs including cytotoxic agents, molecular-targeted agents, and other agents that activate or suppress RIIR. CONCLUSIONS: Our study provides an encyclopedic catalogue of clinically approved drugs based on their effect on RIIR. In ICIs combined radiotherapy, activation of STING-IFN may improve the therapeutic effect and our result could form a biological basis for further clinical trials combining radiotherapy with ICIs.
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spelling pubmed-91744932022-06-09 Comprehensive screening for drugs that modify radiation-induced immune responses Okumura, Masayuki Du, Junyan Kageyama, Shun-Ichiro Yamashita, Riu Hakozaki, Yumi Motegi, Atsushi Hojo, Hidehiro Nakamura, Masaki Hirano, Yasuhiro Okuma, Yusuke Okuma, Hitomi S. Tsuchihara, Katsuya Akimoto, Tetsuo Br J Cancer Article BACKGROUND: Combination therapy based on radiotherapy and immune checkpoint inhibitors (ICIs) was recently reported as effective for various cancers. The radiation-induced immune response (RIIR) is an essential feature in ICI-combined radiotherapy; however, the effects of drugs used concomitantly with RIIR remain unclear. We screened for drugs that can modify RIIR to understand the mutual relationship between radiotherapy and combined drugs in ICI-combined radiotherapy. METHODS: We established a high-throughput system with reporter gene assays for evaluating RIIR, focusing on factors acting downstream of the STING-IRF pathway, which can stimulate cancer cells, T cells, and dendritic cells. We further quantified the effects of 2595 drugs, including those approved by the Food and Drug Administration, on RIIR in vitro. RESULTS: The reporter assay results correlated well with the expression of immune response proteins such as programmed death-ligand 1. This high-throughput system enabled the identification of drugs including cytotoxic agents, molecular-targeted agents, and other agents that activate or suppress RIIR. CONCLUSIONS: Our study provides an encyclopedic catalogue of clinically approved drugs based on their effect on RIIR. In ICIs combined radiotherapy, activation of STING-IFN may improve the therapeutic effect and our result could form a biological basis for further clinical trials combining radiotherapy with ICIs. Nature Publishing Group UK 2022-02-19 2022-06-01 /pmc/articles/PMC9174493/ /pubmed/35184156 http://dx.doi.org/10.1038/s41416-021-01688-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Okumura, Masayuki
Du, Junyan
Kageyama, Shun-Ichiro
Yamashita, Riu
Hakozaki, Yumi
Motegi, Atsushi
Hojo, Hidehiro
Nakamura, Masaki
Hirano, Yasuhiro
Okuma, Yusuke
Okuma, Hitomi S.
Tsuchihara, Katsuya
Akimoto, Tetsuo
Comprehensive screening for drugs that modify radiation-induced immune responses
title Comprehensive screening for drugs that modify radiation-induced immune responses
title_full Comprehensive screening for drugs that modify radiation-induced immune responses
title_fullStr Comprehensive screening for drugs that modify radiation-induced immune responses
title_full_unstemmed Comprehensive screening for drugs that modify radiation-induced immune responses
title_short Comprehensive screening for drugs that modify radiation-induced immune responses
title_sort comprehensive screening for drugs that modify radiation-induced immune responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174493/
https://www.ncbi.nlm.nih.gov/pubmed/35184156
http://dx.doi.org/10.1038/s41416-021-01688-0
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