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The interleukin\u20106 (IL\u20106)\/JAK\/STAT3 signal pathways play multiple regulatory roles in modulating inflammation and immunity in cancers. Polarization of myeloid\u2010derived suppressor cells (MDSCs) is involved in HBV\u2010related immunosuppression and CD8<jats:sup>+<\/jats:sup> T\u2010cell activation through ERK\/IL\u20106\/STAT3. Icaritin is a small molecule that has displayed anticancer activities through IL\u20106\/JAK\/STAT3 pathways in tumor cells and immune cells including CD8<jats:sup>+<\/jats:sup> T cells, MDSCs, neutrophils, and macrophages. This study aimed to confirm icaritin immunomodulation in advanced HBV\u2010related HCC patients with poor prognosis. Immunomodulation of MDSCs was evaluated in BALB\/c mice in vivo. Immunomodulation of serum cytokines and a panel of immune checkpoint proteins were assessed in HBV\u2010related, histologically confirmed HCC patients. Poor prognostic characteristics included HBV infection, bulky tumors, Child\u2010Pugh B classification, and metastasis. Clinical end\u2010points included safety, tumor response, and overall survival (OS). Icaritin treatment\u2010induced dynamics of serum cytokines IL\u20106, IL\u20108, IL\u201010, and tumor necrosis factor\u2010\u03b1, and soluble immune checkpoint proteins TIM3, LAG3, CD28, CD80, and CTLA\u20104 were assessed. No grade III\/IV treatment\u2010related adverse events were observed. Time\u2010to\u2010progression was significantly associated with the prognostic factors. Improved survival was observed in the advanced HCC patients with dynamic changes of cytokines, immune checkpoint proteins, and immune cells. Median OS (329\u2010565\u00a0days) was significantly correlated with baseline hepatitis B surface antigen positivity, cytokines, tumor neoantigens, and <jats:italic>Stenotrophomonas maltophilia<\/jats:italic> infection. Composite biomarker scores of high\u2010level \u03b1\u2010fetoprotein and T helper type I (Th1)\/Th2 cytokines associated with favorable survival warrant further clinical development of icaritin as an alternative immune\u2010modulatory regimen to treat advanced HCC patients with poor prognosis.<\/jats:p>","DOI":"10.1111\/cas.14641","type":"journal-article","created":{"date-parts":[[2020,9,5]],"date-time":"2020-09-05T15:28:02Z","timestamp":1599319682000},"page":"4218-4231","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Icaritin\u2010induced immunomodulatory efficacy in advanced hepatitis B virus\u2010related hepatocellular carcinoma: Immunodynamic biomarkers and overall survival"],"prefix":"10.1111","volume":"111","author":[{"given":"Shu\u2010Kui","family":"Qin","sequence":"first","affiliation":[{"name":"Clinical Oncology Department Nanjing Jinling Hospital Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center Cancer Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Ming Xu","sequence":"additional","affiliation":[{"name":"The 5th Medical Centre Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liang","sequence":"additional","affiliation":[{"name":"Clinical Oncology Department The Affiliated Hospital of Qingdao University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cheng","sequence":"additional","affiliation":[{"name":"Clinical Oncology Department Jilin Cancer Hospital Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Fan","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center Cancer Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center Cancer Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Ye","sequence":"additional","affiliation":[{"name":"Research &amp; Development Department SinoTech Genomics Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Life Science Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Science Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Life Science Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Wei","sequence":"additional","affiliation":[{"name":"Biostatistical Department Tigermed Consulting Co., Ltd. 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