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

作者信息

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

机构信息

Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

出版信息

iScience. 2025 Apr 6;28(5):112364. doi: 10.1016/j.isci.2025.112364. eCollection 2025 May 16.

DOI:10.1016/j.isci.2025.112364
PMID:40292307
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12032931/
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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/25817c86f2b1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/334398b02d2a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/ebf0d86a9bee/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/f1a61aefee3a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/692ad7384a7b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/bc886f6bddae/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/25817c86f2b1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/334398b02d2a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/ebf0d86a9bee/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/f1a61aefee3a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/692ad7384a7b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/bc886f6bddae/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c2/12032931/25817c86f2b1/gr5.jpg

相似文献

[1]
Hepatic iNKT cells facilitate colorectal cancer metastasis by inducing a fibrotic niche in the liver.

iScience. 2025-4-6

[2]
High Frequency of Gamma Interferon-Producing PLZFRORγt Invariant Natural Killer 1 Cells Infiltrating Herpes Simplex Virus 1-Infected Corneas Is Associated with Asymptomatic Ocular Herpesvirus Infection.

J Virol. 2020-4-16

[3]
Early activation and recruitment of invariant natural killer T cells during liver ischemia-reperfusion: the major role of the alarmin interleukin-33.

Front Immunol. 2023

[4]
Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.

Immunity. 2023-1-10

[5]
Combination of NKT14m and Low Dose IL-12 Promotes Invariant Natural Killer T Cell IFN-γ Production and Tumor Control.

Int J Mol Sci. 2020-7-18

[6]
Hyperactivated peripheral invariant natural killer T cells correlate with the progression of HBV-relative liver cirrhosis.

Scand J Immunol. 2019-5-22

[7]
Serpinb1a Is Dispensable for the Development and Cytokine Response of Invariant Natural Killer T Cell Subsets.

Front Immunol. 2020

[8]
Stimulatory lipids accumulate in the mouse liver within 30 min of contact sensitization to facilitate the activation of Naïve iNKT cells in a CD1d-dependent fashion.

Scand J Immunol. 2011-7

[9]
scRNA-Seq and imaging mass cytometry analyses unveil iNKT cells-mediated anti-tumor immunity in pancreatic cancer liver metastasis.

Cancer Lett. 2023-5-1

[10]
Diverse roles of invariant natural killer T cells in liver injury and fibrosis induced by carbon tetrachloride.

Hepatology. 2009-5

引用本文的文献

[1]
Liver metastasis of colorectal cancer: Mechanism and clinical therapy (Review).

Oncol Rep. 2025-10

[2]
Interplay between innate-like T-cells and microRNAs in cancer immunity.

Discov Oncol. 2025-7-28

本文引用的文献

[1]
Innate-like T cells in liver disease.

Trends Immunol. 2024-7

[2]
Mechanisms of metastatic colorectal cancer.

Nat Rev Gastroenterol Hepatol. 2024-9

[3]
Type 1 invariant natural killer T cells in chronic inflammation and tissue fibrosis.

Front Immunol. 2023

[4]
Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis.

Nat Commun. 2023-10-9

[5]
NKG2D-mediated detection of metabolically stressed hepatocytes by innate-like T cells is essential for initiation of NASH and fibrosis.

Sci Immunol. 2023-9-29

[6]
Hepatic inflammatory responses in liver fibrosis.

Nat Rev Gastroenterol Hepatol. 2023-10

[7]
Dictionary learning for integrative, multimodal and scalable single-cell analysis.

Nat Biotechnol. 2024-2

[8]
MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming.

Nat Commun. 2023-4-1

[9]
Immune determinants of the pre-metastatic niche.

Cancer Cell. 2023-3-13

[10]
IL-4 and IL-13: Regulators and Effectors of Wound Repair.

Annu Rev Immunol. 2023-4-26

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