A critical role of STING-triggered tumor-migrating neutrophils for anti-tumor effect of intratumoral cGAMP treatment
| العنوان: | A critical role of STING-triggered tumor-migrating neutrophils for anti-tumor effect of intratumoral cGAMP treatment |
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| المؤلفون: | Syunsuke Yasuda, Marino Nagata, Kensuke Oikawa, Akemi Kosaka, Celis Esteban, Yasuaki Harabuchi, Shohei Harabuchi, Hiroya Kobayashi, Takayuki Ohkuri, Mizuho Ohara, Takumi Kumai, Toshihiro Nagato, Jun Ueda, Hiroshi Funakoshi, Yuki Yajima, Ryusuke Hayashi, Kenzo Ohara |
| المصدر: | Cancer Immunology, Immunotherapy. 70:2301-2312 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, Neutrophils, T-Lymphocytes, Immunology, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Cell Movement, Interferon, Cell Line, Tumor, medicine, Animals, Immunology and Allergy, CXC chemokine receptors, Mice, Knockout, Chemistry, Immunity, Membrane Proteins, Mice, Inbred C57BL, CXCL1, Transplantation, Sting, Oncology, Stimulator of interferon genes, Interferon Type I, Cancer research, Lymph Nodes, Nucleotides, Cyclic, Signal transduction, Signal Transduction, 030215 immunology, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1432-0851 0340-7004 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a34589f75de98c79eb580a8ea5323a7 https://doi.org/10.1007/s00262-021-02864-0 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....6a34589f75de98c79eb580a8ea5323a7 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14320851 03407004 |
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