Hepatic iNKT cells facilitate colorectal cancer metastasis by inducing a fibrotic niche in the liver

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-04-06 DOI:10.1016/j.isci.2025.112364

Marc Nater , Michael Brügger , Virginia Cecconi , Paulo Pereira , Geo Forni , Hakan Köksal , Despoina Dimakou , Michael Herbst , Anna Laura Calvanese , Giulia Lucchiari , Christoph Schneider , Tomas Valenta , Maries van den Broek

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引用次数: 0

Abstract

The liver is an important metastatic organ that contains many innate immune cells, yet little is known about their role in anti-metastatic defense. We investigated how invariant natural killer T (iNKT) cells influence colorectal cancer-derived liver metastasis using different models in immunocompetent mice. We found that hepatic iNKT cells promote metastasis by creating a supportive niche for disseminated cancer cells. Mechanistically, iNKT cells respond to disseminating cancer cells by producing the fibrogenic cytokines interleukin-4 (IL-4) and IL-13 in a T cell receptor-independent manner. Selective abrogation of IL-4 and IL-13 sensing in hepatic stellate cells prevented their transdifferentiation into extracellular matrix-producing myofibroblasts, which hindered metastatic outgrowth of disseminated cancer cells. This study highlights a novel tumor-promoting axis driven by iNKT cells in the initial stages of metastasis.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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