Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis
Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis
SUMMARY The liver is a major metastatic target organ, and little is known about the role of immunity in controlling hepatic metastases. Here, we discovered that the concerted and non-redundant action of two innate lymphocyte subpopulations, conventional NK cells (cNKs) and tissue-resident type I Innate Lymphoid Cells (trILC1s), is essential for anti-metastatic defense. Using different preclinical models for liver metastasis, we found that trILC1 control metastatic seeding, whereas cNKs restrain outgrowth. The antimetastatic activity of cNKs is regulated in a tumor type-specific fashion. Thereby, individual cancer cell lines orchestrate the emergence of cNK subsets with unique phenotypic and functional traits. Understanding cancer-cell- as well as innate-cell-intrinsic factors will allow the exploitation of hepatic innate cells for development of novel cancer therapies. SignificanceInnate lymphoid cells hold great promise for the treatment of metastases. Development of effective therapies based on these versatile immune cells, however, is hampered by our limited knowledge of their behavior in the metastatic niche. Here, we describe that defense against liver metastasis requires the collaboration between two innate lymphocyte subsets, conventional NK cells (cNKs) and tissue-resident type I innate lymphoid cells (trILC1s). We show that different cancers generate their own particular metastatic niche inducing specific changes in cNKs and trILC1s. Further, we uncover specific cNK subsets that can be manipulated to improve their anti-metastatic potential. Our work contributes to understanding how cancer-specific factors and hepatic innate lymphocytes exert mutual influence and how this can be exploited for therapeutic purposes. HighlightscNKs and trILC1s collaborate to control hepatic metastasistrILC1s restrict seeding and cNKs control outgrowth of cancer cells in the liverIndividual cancer cell lines orchestrate a distinct metastatic nicheThe metastatic niche dictates the phenotype and function of cNKs
Lucchiari Giulia、Nater Marc、van den Broek Maries、Litscher Gioana、Vermeer Marijne、Gschwend Julia、Ducimeti¨¨re Laura、Moor Andreas E.、Nu?ez Nicol¨￠s Gonzalo、Tugues Sonia、Becher Burkhard、Burri Dominik、Heeb Laura、Wyss Laura
Tumor Immunology, Institute of Experimental Immunology, University of ZurichTumor Immunology, Institute of Experimental Immunology, University of ZurichTumor Immunology, Institute of Experimental Immunology, University of ZurichInnate Lymphoid Cells and Cancer, Institute of Experimental Immunology, University of ZurichInnate Lymphoid Cells and Cancer, Institute of Experimental Immunology, University of ZurichInnate Lymphoid Cells and Cancer, Institute of Experimental Immunology, University of ZurichInnate Lymphoid Cells and Cancer, Institute of Experimental Immunology, University of ZurichInstitute of Molecular Cancer Research, University of Zurich||Department of Biosystems Science and Engineering (D-BSSE)Inflammation Research, Institute of Experimental Immunology, University of ZurichInnate Lymphoid Cells and Cancer, Institute of Experimental Immunology, University of ZurichInflammation Research, Institute of Experimental Immunology, University of ZurichTumor Immunology, Institute of Experimental Immunology, University of Zurich||Computational and Systems Biology, Biozentrum University of BaselInnate Lymphoid Cells and Cancer, Institute of Experimental Immunology, University of ZurichTumor Immunology, Institute of Experimental Immunology, University of Zurich
肿瘤学基础医学
LivermetastasisNK cellsILC1stumor microenvironment
Lucchiari Giulia,Nater Marc,van den Broek Maries,Litscher Gioana,Vermeer Marijne,Gschwend Julia,Ducimeti¨¨re Laura,Moor Andreas E.,Nu?ez Nicol¨￠s Gonzalo,Tugues Sonia,Becher Burkhard,Burri Dominik,Heeb Laura,Wyss Laura.Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis[EB/OL].(2025-03-28)[2025-04-24].https://www.biorxiv.org/content/10.1101/2020.07.17.206433.点此复制
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