期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2026271118
关键词
innate lymphocytes metastatic surveillance tissue-resident ILC1s conventional NK cells
资金
- Swiss National Science Foundation [CRSII5_177208, 310030_175565, PR00P3_179775, 316030_150768, 310030_146130]
- Swiss Cancer League [KLS-4098-02-2017, KFS-4431-02-2018]
- Promedica Stiftung
- University of Zurich (University Research Priority Project Translational Cancer Research)
- Monique-Dornonville-de-la-Cour Foundation Zurich
- Swiss National Science Foundation (SNF) [310030_175565, PR00P3_179775] Funding Source: Swiss National Science Foundation (SNF)
This study found that innate lymphocyte subpopulations cNKs and trILC1s play nonredundant roles in controlling liver metastasis seeding and outgrowth, respectively, and may contribute to developing therapies involving hepatic innate cells.
The liver isa major metastatic target organ, and little is known about the role of immunity in controlling hepatic metastases. Here, we discovered that the concerted and nonredundant action of two innate lymphocyte subpopulations, conventional natural killer cells (cNKs) and tissue-resident type I innate lymphoid cells (trILC1s), is es-sential for antimetastatic defense. Using different preclinical models for liver metastasis, we found that trILC1 controls metastatic seeding, whereas cNKs restrain outgrowth. Whereas the killing capacity of trILC1s was not affected by the metastatic microenvironment, the phenotype and function of cNK cells were affected in a cancer type- specific fashion. Thus, individual cancer cell lines orchestrate the emer-gence of unique cNK subsets, which respond differently to tumor-derived factors. Our findings will contribute to the development of therapies for liver metastasis involving hepatic innate cells.
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