ArticleTranslational oncology2026
Interleukin 35 promotes progression of hepatocellular carcinoma by recruiting neutrophils.
Article in Translational oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundA growing number of therapeutic strategies against hepatocellular carcinoma (HCC) have emerged. However, their efficacy remains limited. This study investigated the mechanism of interleukin-35 (IL-35) in the progression of HCC and its potential application in HCC treatment.
methodsThe expression of IL-35,Gp130 ,IL12-Rβ2, CCL3,etc. in HCC tissues was detected by immunohistochemistry(IHC), and the expression of IL-35 in HCC cell lines was detected by fluorescence assay. Kaplan-Meier survival analysis of IL-35 and its receptor in relation to overall survival(OS) and recurrence free survival(RFS) in patients with HCC. The mouse subcutaneous tumor models to study the effects of IL-35 on HCC growth and immune cells. Western blot were used to detect the expression IL-35, CCL3, FGF2, and flow cytometric plot were performed to explore the immune cells infiltration in the tumor tissue.
resultsHigh expression of IL-35 in patients with HCC was associated with poor prognosis. Furthermore, IL-35 could facilitate tumor progression by affecting neutrophil infiltration, angiogenesis, and CD8+ T-cell infiltration. Additionally, CCL3 was a key factor mediating the recruitment of neutrophils by IL-35. FGF2 derived from neutrophils stimulated by IL-35 promoted intratumoral angiogenesis. IL-35 also facilitated the adhesion of tumors to endothelial cells, with neutrophils further enhancing this effect both. Anti-IL-35 antibody combined with anti-PD1 antibody significantly enhanced which therapeutic effect in HCC.
conclusionsOur data show that the high expression of IL-35 in patients with HCC is an important tumor promoter. Combined treatment with anti-IL-35 and anti-PD1 antibodies have potential therapeutic effect against HCC.
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