Cell Reports (Mar 2025)

Inflammatory cytokines mediate the induction of and awakening from metastatic dormancy

  • 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

DOI
https://doi.org/10.1016/j.celrep.2025.115388
Journal volume & issue
Vol. 44, no. 3
p. 115388

Abstract

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Summary: 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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