{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:33:54Z","timestamp":1792704834151,"version":"4.5.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T00:00:00Z","timestamp":1624147200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      GS\u20109688 (selgantolimod) is a toll\u2010like receptor 8 agonist in clinical development for the treatment of chronic hepatitis B (CHB). Antiviral activity of GS\u20109688 has previously been evaluated\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      in HBV\u2010infected hepatocytes and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      in the woodchuck model of CHB. Here we evaluated the potential of GS\u20109688 to boost responses contributing to viral control and to modulate regulatory mediators.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      We characterized the effect of GS\u20109688 on immune cell subsets\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      in peripheral blood mononuclear cells of healthy controls and patients with CHB. GS\u20109688 activated dendritic cells and mononuclear phagocytes to produce IL\u201012 and other immunomodulatory mediators, inducing a comparable cytokine profile in healthy controls and patients with CHB. GS\u20109688 increased the frequency of activated natural killer (NK) cells, mucosal\u2010associated invariant T cells, CD4\n                      <jats:sup>+<\/jats:sup>\n                      follicular helper T cells, and, in about 50% of patients, HBV\u2010specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells expressing interferon\u2010\u03b3. Moreover,\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      stimulation with GS\u20109688 induced NK\u2010cell expression of interferon\u2010\u03b3 and TNF\u2010\u03b1, and promoted hepatocyte lysis. We also assessed whether GS\u20109688 inhibited immunosuppressive cell subsets that might enhance antiviral efficacy. Stimulation with GS\u20109688 reduced the frequency of CD4\n                      <jats:sup>+<\/jats:sup>\n                      regulatory T cells and monocytic myeloid\u2010derived suppressor cells (MDSCs). Residual MDSCs expressed higher levels of negative immune regulators, galectin\u20109 and programmed death\u2010ligand 1. Conversely, GS\u20109688 induced an expansion of immunoregulatory TNF\u2010related apoptosis\u2010inducing ligand\n                      <jats:sup>+<\/jats:sup>\n                      NK cells and degranulation of arginase\u2010I\n                      <jats:sup>+<\/jats:sup>\n                      polymorphonuclear MDSCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      GS\u20109688 induces cytokines in human peripheral blood mononuclear cells that are able to activate antiviral effector function by multiple immune mediators (HBV\u2010specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, CD4\n                      <jats:sup>+<\/jats:sup>\n                      follicular helper T cells, NK cells, and mucosal\u2010associated invariant T cells). Although reducing the frequency of some immunoregulatory subsets, it enhances the immunosuppressive potential of others, highlighting potential biomarkers and immunotherapeutic targets to optimize the antiviral efficacy of GS\u20109688.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.31695","type":"journal-article","created":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T02:47:43Z","timestamp":1608950863000},"page":"55-71","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":97,"title":["Therapeutic Potential of TLR8 Agonist GS\u20109688 (Selgantolimod) in Chronic Hepatitis B: Remodeling of Antiviral and Regulatory Mediators"],"prefix":"10.1097","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3663-1253","authenticated-orcid":false,"given":"Oliver E.","family":"Amin","sequence":"first","affiliation":[{"name":"Division of Infection & Immunity,Institute of Immunity & 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City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Pattabiraman","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Chu","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Micolochick Steuer","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Lehar","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"Peiser","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.,Foster 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