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

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...

Full description

Saved in:

Bibliographic Details
Published in:	Cancer science Vol. 112; no. 12; pp. 5088 - 5099
Main Authors:	Miyagi, Shouhei, Watanabe, Takahiro, Hara, Yuya, Arata, Masataka, Uddin, Md. Kamal, Mantoku, Keisuke, Sago, Ken, Yanagi, Yusuke, Suzuki, Takeshi, Masud, H. M. Abdullah Al, Kawada, Jun‐ichi, Nakamura, Shigeo, Miyake, Yasuyuki, Sato, Yoshitaka, Murata, Takayuki, Kimura, Hiroshi
Format:	Journal Article
Language:	English
Published:	England John Wiley & Sons, Inc 01-12-2021 John Wiley and Sons Inc
Subjects:	Adaptor proteins Animals Antibodies Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Cell growth Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Cell Transformation, Viral - drug effects cGAS Deoxyribonucleic acid DNA EBV‐LPD Epstein-Barr virus Epstein-Barr Virus Infections - drug therapy Epstein-Barr Virus Infections - immunology Gene expression Genetic transformation HEK293 Cells Herpesvirus 4, Human Humans Immunoproliferative diseases Infections Innate immunity Interferon Jurkat Cells Kinases Leukocytes (mononuclear) Lymphocytes Lymphocytes B Lymphocytes T Lymphoma, B-Cell - immunology Lymphoma, B-Cell - prevention & control Lymphoma, B-Cell - virology Membrane Proteins - antagonists & inhibitors Mice Original PAMPs Pathogens Peripheral blood mononuclear cells Signal transduction STING Survival Analysis T-Lymphocytes - drug effects T-Lymphocytes - metabolism Therapeutic targets Treatment Outcome Tumorigenesis Tumorigenicity Tumors Xenograft Model Antitumor Assays cGAS PAMPs STING Epstein-Barr virus EBV-LPD
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. Treatment with STING inhibitor, C‐176, suppressed the tumor formation in a mouse model of EBV LPDs. Although inhibitor treatment with B cells in vitro alone did not affect EBV transformation, the suppression of EBV‐induced transformation was observed in the presence of T cells
Bibliography:	Shouhei Miyagi and Takahiro Watanabe contributed equally to this study. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1347-9032 1349-7006
DOI:	10.1111/cas.15152