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CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes

Activation of STING signaling plays an important role in anti-tumor immunity, and we previously reported the anti-tumor effects of STING through accumulation of M1-like macrophages in tumor tissue treated with a STING agonist. However, myeloid cells express SIRPα, an inhibitory receptor for phagocyt...

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Autores principales: Kosaka, Akemi, Ishibashi, Kei, Nagato, Toshihiro, Kitamura, Hidemitsu, Fujiwara, Yukio, Yasuda, Syunsuke, Nagata, Marino, Harabuchi, Shohei, Hayashi, Ryusuke, Yajima, Yuki, Ohara, Kenzo, Kumai, Takumi, Aoki, Naoko, Komohara, Yoshihiro, Oikawa, Kensuke, Harabuchi, Yasuaki, Kitada, Masahiro, Kobayashi, Hiroya, Ohkuri, Takayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480673/
https://www.ncbi.nlm.nih.gov/pubmed/34559187
http://dx.doi.org/10.1084/jem.20200792
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author Kosaka, Akemi
Ishibashi, Kei
Nagato, Toshihiro
Kitamura, Hidemitsu
Fujiwara, Yukio
Yasuda, Syunsuke
Nagata, Marino
Harabuchi, Shohei
Hayashi, Ryusuke
Yajima, Yuki
Ohara, Kenzo
Kumai, Takumi
Aoki, Naoko
Komohara, Yoshihiro
Oikawa, Kensuke
Harabuchi, Yasuaki
Kitada, Masahiro
Kobayashi, Hiroya
Ohkuri, Takayuki
author_facet Kosaka, Akemi
Ishibashi, Kei
Nagato, Toshihiro
Kitamura, Hidemitsu
Fujiwara, Yukio
Yasuda, Syunsuke
Nagata, Marino
Harabuchi, Shohei
Hayashi, Ryusuke
Yajima, Yuki
Ohara, Kenzo
Kumai, Takumi
Aoki, Naoko
Komohara, Yoshihiro
Oikawa, Kensuke
Harabuchi, Yasuaki
Kitada, Masahiro
Kobayashi, Hiroya
Ohkuri, Takayuki
author_sort Kosaka, Akemi
collection PubMed
description Activation of STING signaling plays an important role in anti-tumor immunity, and we previously reported the anti-tumor effects of STING through accumulation of M1-like macrophages in tumor tissue treated with a STING agonist. However, myeloid cells express SIRPα, an inhibitory receptor for phagocytosis, and its receptor, CD47, is overexpressed in various cancer types. Based on our findings that breast cancer patients with highly expressed CD47 have poor survival, we evaluated the therapeutic efficacy and underlying mechanisms of combination therapy with the STING ligand cGAMP and an antagonistic anti-CD47 mAb using E0771 mouse breast cancer cells. Anti-CD47 mAb monotherapy did not suppress tumor growth in our setting, whereas cGAMP and anti-CD47 mAb combination therapy inhibited tumor growth. The combination therapy enhanced phagocytosis of tumor cells and induced systemic anti-tumor immune responses, which rely on STING and type I IFN signaling. Taken together, our findings indicate that coadministration of cGAMP and an antagonistic anti-CD47 mAb may be promising for effective cancer immunotherapy.
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spelling pubmed-84806732022-05-01 CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes Kosaka, Akemi Ishibashi, Kei Nagato, Toshihiro Kitamura, Hidemitsu Fujiwara, Yukio Yasuda, Syunsuke Nagata, Marino Harabuchi, Shohei Hayashi, Ryusuke Yajima, Yuki Ohara, Kenzo Kumai, Takumi Aoki, Naoko Komohara, Yoshihiro Oikawa, Kensuke Harabuchi, Yasuaki Kitada, Masahiro Kobayashi, Hiroya Ohkuri, Takayuki J Exp Med Article Activation of STING signaling plays an important role in anti-tumor immunity, and we previously reported the anti-tumor effects of STING through accumulation of M1-like macrophages in tumor tissue treated with a STING agonist. However, myeloid cells express SIRPα, an inhibitory receptor for phagocytosis, and its receptor, CD47, is overexpressed in various cancer types. Based on our findings that breast cancer patients with highly expressed CD47 have poor survival, we evaluated the therapeutic efficacy and underlying mechanisms of combination therapy with the STING ligand cGAMP and an antagonistic anti-CD47 mAb using E0771 mouse breast cancer cells. Anti-CD47 mAb monotherapy did not suppress tumor growth in our setting, whereas cGAMP and anti-CD47 mAb combination therapy inhibited tumor growth. The combination therapy enhanced phagocytosis of tumor cells and induced systemic anti-tumor immune responses, which rely on STING and type I IFN signaling. Taken together, our findings indicate that coadministration of cGAMP and an antagonistic anti-CD47 mAb may be promising for effective cancer immunotherapy. Rockefeller University Press 2021-09-24 /pmc/articles/PMC8480673/ /pubmed/34559187 http://dx.doi.org/10.1084/jem.20200792 Text en © 2021 Kosaka et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Kosaka, Akemi
Ishibashi, Kei
Nagato, Toshihiro
Kitamura, Hidemitsu
Fujiwara, Yukio
Yasuda, Syunsuke
Nagata, Marino
Harabuchi, Shohei
Hayashi, Ryusuke
Yajima, Yuki
Ohara, Kenzo
Kumai, Takumi
Aoki, Naoko
Komohara, Yoshihiro
Oikawa, Kensuke
Harabuchi, Yasuaki
Kitada, Masahiro
Kobayashi, Hiroya
Ohkuri, Takayuki
CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes
title CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes
title_full CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes
title_fullStr CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes
title_full_unstemmed CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes
title_short CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes
title_sort cd47 blockade enhances the efficacy of intratumoral sting-targeting therapy by activating phagocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480673/
https://www.ncbi.nlm.nih.gov/pubmed/34559187
http://dx.doi.org/10.1084/jem.20200792
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