{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:34:06Z","timestamp":1790728446095,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T00:00:00Z","timestamp":1603670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin City","doi-asserted-by":"publisher","award":["18JCYBJC26400"],"award-info":[{"award-number":["18JCYBJC26400"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,13]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Hepatic inflammatory response is a risk factor for liver cancer initiation and progression. Interleukin (IL)-35 is the newest member of the IL-12 cytokine family, and has been reported to play an essential role in the immunosuppressive liver microenvironment. Herein we focus on the expression profiles of IL-35 in hepatocellular carcinoma (HCC) and effects on local immune status. HCC transcriptome array data were downloaded from Gene Expression Omnibus (GEO). Analysis was performed by BRB-Array Tools and Ingenuity Pathway Analysis (IPA) software. Serum IL-35 level was detected by AimPlet bead-based immunoassay. In-situ IL-35 detection was performed by immunohistochemical staining and Western blot. The n-vitro effect of IL-35 on CD4+ or CD8+ T cell function was detected by flow cytometry. Our results showed that there were large amounts of IL-35 expressed in HCC serum and tumor tissues. IL-35 expression affects the transcript of thousands of genes, most differentially expressed genes (DEGs), in tumor tissues correlated with T cell immunity. The IL-35 high-expression group exhibited enhancement of regulatory T cells (Tregs) and impairment of cytolytic T cells. In-vitro experiments proved that exogenous IL-35 stimulated the expression of programmed cell death 1 (PD-1) and lymphocyte activation gene-3 (LAG3) in CD4+ and CD8+ T cells. In addition, the stimulating effect was time-dependent. Furthermore, IL-35 inhibited interferon (IFN)-\u03b3 secretion by CD4+ and CD8+ T cells. Elevated IL-35 had an immune suppressive role in HCC tumor microenvironments through affecting inhibitor receptor expression and cytokine secretion of CD4+ and CD8+ T cells. Dissection of the precise targets and underlying molecular mechanisms would mean alternative treatments for HCC patients.<\/jats:p>","DOI":"10.1111\/cei.13535","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T09:32:01Z","timestamp":1602149521000},"page":"219-229","source":"Crossref","is-referenced-by-count":28,"title":["Interleukin-35 has a tumor-promoting role in hepatocellular carcinoma"],"prefix":"10.1093","volume":"203","author":[{"given":"X","family":"Liu","sequence":"first","affiliation":[{"name":"Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3418-6873","authenticated-orcid":false,"given":"N","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,26]]},"reference":[{"key":"2021121023211907900_cei13535-bib-0001","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1053\/j.gastro.2016.11.048","article-title":"Liver cancer cell of origin, molecular class, and effects on patient prognosis","volume":"152","author":"Sia","year":"2017","journal-title":"Gastroenterology"},{"key":"2021121023211907900_cei13535-bib-0002","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"2021121023211907900_cei13535-bib-0003","doi-asserted-by":"crossref","first-page":"3151","DOI":"10.3748\/wjg.v25.i25.3151","article-title":"Hepatocellular carcinoma: Mechanisms of progression and immunotherapy","volume":"25","author":"Jiang","year":"2019","journal-title":"World J Gastroenterol"},{"key":"2021121023211907900_cei13535-bib-0004","doi-asserted-by":"crossref","first-page":"256","DOI":"10.21037\/jgo.2016.09.07","article-title":"Hepatocellular carcinoma (HCC): beyond sorafenib-chemotherapy","volume":"8","author":"Kim","year":"2017","journal-title":"J Gastrointest Oncol"},{"key":"2021121023211907900_cei13535-bib-0005","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jhep.2019.08.014","article-title":"The immunobiology of hepatocellular carcinoma in humans and mice. 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