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28.01.2021 | Original Article

A critical role of STING-triggered tumor-migrating neutrophils for anti-tumor effect of intratumoral cGAMP treatment

verfasst von: Marino Nagata, Akemi Kosaka, Yuki Yajima, Syunsuke Yasuda, Mizuho Ohara, Kenzo Ohara, Shohei Harabuchi, Ryusuke Hayashi, Hiroshi Funakoshi, Jun Ueda, Takumi Kumai, Toshihiro Nagato, Kensuke Oikawa, Yasuaki Harabuchi, Celis Esteban, Takayuki Ohkuri, Hiroya Kobayashi

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 8/2021

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Abstract

Stimulator of interferon genes (STING) contributes to anti-tumor immunity by activating antigen-presenting cells and inducing mobilization of tumor-specific T cells. A role for tumor-migrating neutrophils in the anti-tumor effect of STING-activating therapy has not been defined. We used mouse tumor transplantation models for assessing neutrophil migration into the tumor triggered by intratumoral treatment with STING agonist, 2′3′-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Intratumoral STING activation with cGAMP enhanced neutrophil migration into the tumor in an NF-κB/CXCL1/2-dependent manner. Blocking the neutrophil migration by anti-CXCR2 monoclonal antibody impaired T cell activation in tumor-draining lymph nodes (dLNs) and efficacy of intratumoral cGAMP treatment. Moreover, the intratumoral cGAMP treatment did not show any anti-tumor effect in type I interferon (IFN) signal-impaired mice in spite of enhanced neutrophil accumulation in the tumor. These results suggest that both neutrophil migration and type I interferon (IFN) induction by intratumoral cGAMP treatment were critical for T-cell activation of dLNs and the anti-tumor effect. In addition, we also performed in vitro analysis showing enhanced cytotoxicity of neutrophils by IFN-β1. Extrinsic STING activation triggers anti-tumor immune responses by recruiting and activating neutrophils in the tumor via two signaling pathways, CXCL1/2 and type I IFNs.

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Titel: A critical role of STING-triggered tumor-migrating neutrophils for anti-tumor effect of intratumoral cGAMP treatment
verfasst von: Marino Nagata
Akemi Kosaka
Yuki Yajima
Syunsuke Yasuda
Mizuho Ohara
Kenzo Ohara
Shohei Harabuchi
Ryusuke Hayashi
Hiroshi Funakoshi
Jun Ueda
Takumi Kumai
Toshihiro Nagato
Kensuke Oikawa
Yasuaki Harabuchi
Celis Esteban
Takayuki Ohkuri
Hiroya Kobayashi
Publikationsdatum: 28.01.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 8/2021
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-021-02864-0

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

A critical role of STING-triggered tumor-migrating neutrophils for anti-tumor effect of intratumoral cGAMP treatment

Abstract

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Springer Medizin

Abstract

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