Inflammatory cytokines mediate the induction of and awakening from metastatic dormancy.

IF 6.9 1区生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2025-03-25 Epub Date: 2025-03-01 DOI:10.1016/j.celrep.2025.115388

Paulo Pereira, Joshua Panier, Marc Nater, Michael Herbst, Anna Laura Calvanese, Hakan Köksal, Héctor Castañón, Virginia Cecconi, Paulino Tallón de Lara, Steve Pascolo, Maries van den Broek

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Abstract

Metastases arise from disseminated cancer cells (DCCs) that detach from the primary tumor and seed distant organs. There, quiescent DCCs can survive for an extended time, a state referred to as metastatic dormancy. The mechanisms governing the induction, maintenance, and awakening from metastatic dormancy are unclear. We show that the differentiation of dormancy-inducing CD8⁺ T cells requires CD4⁺ T cell help and that interferon (IFN)γ directly induces dormancy in DCCs. The maintenance of metastatic dormancy, however, is independent of T cells. Instead, awakening from dormancy requires an inflammatory signal, and we identified CD4⁺ T cell-derived interleukin (IL)-17A as an essential wake-up signal for dormant DCCs in the lungs. Thus, the induction of and awakening from metastatic dormancy require an external stimulus, while the maintenance of dormancy does not rely on continuous surveillance by lymphocytes.

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炎症细胞因子介导转移性休眠的诱导和唤醒。

转移发生于播散性癌细胞（DCCs），它们从原发肿瘤中分离出来，扩散到远处器官。在那里，静止的DCCs可以存活较长时间，这种状态被称为转移性休眠。诱导、维持和从转移性休眠中唤醒的机制尚不清楚。我们发现诱导休眠的CD8+ T细胞的分化需要CD4+ T细胞的帮助，干扰素(IFN)γ直接诱导DCCs的休眠。然而，转移性休眠的维持是独立于T细胞的。相反，从休眠中唤醒需要炎症信号，我们发现CD4+ T细胞衍生的白细胞介素(IL)-17A是肺部休眠dcc的重要唤醒信号。因此，转移性休眠的诱导和唤醒需要外部刺激，而休眠的维持不依赖于淋巴细胞的持续监测。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.