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

Autor: Miyagi S; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Department of Pathology and Laboratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan., Watanabe T; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Hara Y; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Arata M; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Uddin MK; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Mantoku K; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Sago K; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Yanagi Y; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Suzuki T; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Masud HMAA; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Department of Microbiology, Faculty of Biological Sciences, University of Chittagong, Chattogram, Bangladesh., Kawada JI; Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan., Nakamura S; Department of Pathology and Laboratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan., Miyake Y; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Sato Y; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan., Murata T; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Japan., Kimura H; Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2021 Dec; Vol. 112 (12), pp. 5088-5099. Date of Electronic Publication: 2021 Oct 11.
DOI: 10.1111/cas.15152
Abstrakt: 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.
(© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
Databáze: MEDLINE
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