ArticleBritish journal of cancer2026
IL-33 released during liver resection facilitates intrahepatic cholangiocarcinoma growth via cytokine secretion in cancer-associated fibroblasts.
Article in British journal of cancer, 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
backgroundWe previously reported that IL-33 released during hepatectomy contributes to cytokine-facilitated iCCA tumor growth. However, the underlying mechanisms of the tumor microenvironment remain unexplored. In this study, we aimed to elucidate the impact of IL-33 on cancer-associated fibroblasts (CAFs).
methodsThe abundance of IL-33-positive cells and alpha-SMA-positive fibroblasts (myoCAFs) was evaluated using resected specimens. Next-generation sequencing (NGS) was performed for comprehensive expression analysis. The effects of IL-33 stimulation on CAFs were investigated in vitro and in vivo using human and murine iCCA cell lines, as well as fibroblasts extracted from resected specimens.
resultsIL-33-positive cells and myoCAFs were significant risk factors for intrahepatic recurrence. NGS analysis revealed significant upregulation of various cytokines in cases with high number of IL-33-positive cells. The conditioned medium obtained from fibroblasts stimulated with IL-33 enhanced the proliferation and migration of iCCA cell lines. Among the cytokines that were increased by IL-33 stimulation in vitro, IL-6 was suspected to be the dominant. In a murine syngraft model, hepatectomy led to an increased subcutaneous tumor volume by releasing IL-33, whereas IL-6 blockade suppressed this growth.
conclusionsThis study indicated that IL-33 facilitates iCCA growth through fibroblast activation and is associated with intrahepatic recurrence.
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