A STING inhibitor suppresses EBV-induced B cell transformation and lymphomagenesis

Shouhei Miyagi; Takahiro Watanabe; Yuya Hara; Masataka Arata; Md Kamal Uddin; Keisuke Mantoku; Ken Sago; Yusuke Yanagi; Takeshi Suzuki; H. M.Abdullah Al Masud; Jun ichi Kawada; Shigeo Nakamura; Yasuyuki Miyake; Yoshitaka Sato; Takayuki Murata; Hiroshi Kimura

doi:10.1111/cas.15152

A STING inhibitor suppresses EBV-induced B cell transformation and lymphomagenesis

Shouhei Miyagi, Takahiro Watanabe, Yuya Hara, Masataka Arata, Md Kamal Uddin, Keisuke Mantoku, Ken Sago, Yusuke Yanagi, Takeshi Suzuki, H. M.Abdullah Al Masud, Jun ichi Kawada, Shigeo Nakamura, Yasuyuki Miyake, Yoshitaka Sato, Takayuki Murata, Hiroshi Kimura

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

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.

Original language	English
Pages (from-to)	5088-5099
Number of pages	12
Journal	Cancer science
Volume	112
Issue number	12
DOIs	https://doi.org/10.1111/cas.15152
Publication status	Published - 12-2021
Externally published	Yes

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/cas.15152

Cite this

@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 = "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",

}

TY - JOUR

T1 - A STING inhibitor suppresses EBV-induced B cell transformation and lymphomagenesis

AU - Miyagi, Shouhei

AU - Watanabe, Takahiro

AU - Hara, Yuya

AU - Arata, Masataka

AU - Uddin, Md Kamal

AU - Mantoku, Keisuke

AU - Sago, Ken

AU - Yanagi, Yusuke

AU - Suzuki, Takeshi

AU - Masud, H. M.Abdullah Al

AU - Kawada, Jun ichi

AU - Nakamura, Shigeo

AU - Miyake, Yasuyuki

AU - Sato, Yoshitaka

AU - Murata, Takayuki

AU - Kimura, Hiroshi

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85116775164

UR - https://www.scopus.com/inward/citedby.url?scp=85116775164&partnerID=8YFLogxK

U2 - 10.1111/cas.15152

DO - 10.1111/cas.15152

M3 - Article

C2 - 34609775

AN - SCOPUS:85116775164

SN - 1347-9032

VL - 112

SP - 5088

EP - 5099

JO - Cancer science

JF - Cancer science

IS - 12

ER -

A STING inhibitor suppresses EBV-induced B cell transformation and lymphomagenesis

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this