@article{f46ad4caea1148dea7c1e75910f21228,
title = "A STING inhibitor suppresses EBV-induced B cell transformation and lymphomagenesis",
abstract = "Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD) is frequently fatal. Innate immunity plays a key role in protecting against pathogens and cancers. The stimulator of interferon genes (STING) is regarded as a key adaptor protein allowing DNA sensors recognizing exogenous cytosolic DNA to activate the type I interferon signaling cascade. In terms of EBV tumorigenicity, the role of STING remains elusive. Here we showed that treatment with the STING inhibitor, C-176, suppressed EBV-induced transformation in peripheral blood mononuclear cells. In an EBV-LPD mouse model, C-176 treatment also inhibited tumor formation and prolonged survival. Treatment with B cells alone did not affect EBV transformation, but suppression of EBV-induced transformation was observed in the presence of T cells. Even without direct B cell-T cell contact in a transwell system, the inhibitor reduced the transformation activity, indicating that intercellular communication by humoral factors was critical to prevent EBV-induced transformation. These findings suggest that inhibition of STING signaling pathway with C-176 could be a new therapeutic target of EBV-LPD.",
author = "Shouhei Miyagi and Takahiro Watanabe and Yuya Hara and Masataka Arata and Uddin, {Md Kamal} and Keisuke Mantoku and Ken Sago and Yusuke Yanagi and Takeshi Suzuki and Masud, {H. M.Abdullah Al} and Kawada, {Jun ichi} and Shigeo Nakamura and Yasuyuki Miyake and Yoshitaka Sato and Takayuki Murata and Hiroshi Kimura",
note = "Funding Information: We thank Drs. Eric Johannsen, Wolfgang Hammerschmidt, Henri-Jacques Delecluse, and Teru Kanda for materials. We also acknowledge Yoshitaka Adachi of the Department of Hematology and Oncology, Nagoya University Graduate School of Medicine for technical support of T cell expansion; Daisuke Sugiyama of the Department of Immunology, Nagoya University Graduate School of Medicine for technical support for in vitro immunological assays. We thank all the members of our laboratory for their assistance. Histological analysis and imaging analyses were carried out in the Division for Medical Research Engineering, Nagoya University Graduate School of Medicine. This study was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (JP18K15165 to TW, and 19K22560 and 20H03493 to HK), and grants from the Aichi Cancer Research Foundation; Kyousaidan; Nasu Research Foundation; Hori Sciences and Arts Foundation to TW and the Uehara Memorial Foundation; the Chemo-Sero-Therapeutic Research Institute to HK and the Precursory Research for Embryonic Science and Technology (PRESTO) from the Japan Agency for Medical Research and Development (AMED) (Grant No. JPMJPR19H5) to YS. Funding Information: We thank Drs. Eric Johannsen, Wolfgang Hammerschmidt, Henri‐Jacques Delecluse, and Teru Kanda for materials. We also acknowledge Yoshitaka Adachi of the Department of Hematology and Oncology, Nagoya University Graduate School of Medicine for technical support of T cell expansion; Daisuke Sugiyama of the Department of Immunology, Nagoya University Graduate School of Medicine for technical support for in vitro immunological assays. We thank all the members of our laboratory for their assistance. Histological analysis and imaging analyses were carried out in the Division for Medical Research Engineering, Nagoya University Graduate School of Medicine. This study was supported by Grants‐in‐Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (JP18K15165 to TW, and 19K22560 and 20H03493 to HK), and grants from the Aichi Cancer Research Foundation; Kyousaidan; Nasu Research Foundation; Hori Sciences and Arts Foundation to TW and the Uehara Memorial Foundation; the Chemo‐Sero‐Therapeutic Research Institute to HK and the Precursory Research for Embryonic Science and Technology (PRESTO) from the Japan Agency for Medical Research and Development (AMED) (Grant No. JPMJPR19H5) to YS. Funding Information: H. Kimura and Y. Sato were supported by grants from Bristol Myers Squibb and Merck Sharp & Dohme, respectively. All other authors have no conflicts of interest directly relevant to the content of this article. Publisher Copyright: {\textcopyright} 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",
year = "2021",
month = dec,
doi = "10.1111/cas.15152",
language = "English",
volume = "112",
pages = "5088--5099",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "12",
}