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

Cancer Sci. 2021 Dec;112(12):5088-5099. doi: 10.1111/cas.15152. Epub 2021 Oct 11.


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.

Keywords: EBV-LPD; Epstein-Barr virus; PAMPs; STING; cGAS.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell Transformation, Viral / drug effects*
  • Epstein-Barr Virus Infections / drug therapy*
  • Epstein-Barr Virus Infections / immunology
  • HEK293 Cells
  • Herpesvirus 4, Human
  • Humans
  • Jurkat Cells
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / prevention & control*
  • Lymphoma, B-Cell / virology
  • Membrane Proteins / antagonists & inhibitors*
  • Mice
  • Survival Analysis
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Treatment Outcome
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Membrane Proteins
  • STING1 protein, human