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<p>Liver metastases are frequent and challenging to treat owing to the liver’s metabolically active and immune-tolerant environment. However, how cancer cells exploit nutrient availability in the liver to evade immune surveillance remains unknown. Here we show that cancer cells use the palmitate availability in the liver to impair the neutrophil antitumour function. Mechanistically, we find that breast and colorectal cancer cells metastasizing to the liver, but not the lung, require the palmitoyltransferase 17 (DHHC17, gene name <i>ZDHHC17</i>) to stabilize laminin-511 enabling its secretion. In turn, neutrophils in the liver metastasis environment respond to laminin-511 by decreasing their cancer cell-killing capacity. Consistently, silencing <i>ZDHHC17</i> in cancer cells decreases liver metastases only in the presence of neutrophils, while metastasis growth is restored in <i>ZDHHC17</i>-silenced metastases upon injection of laminin-511 or inhibition of neutrophil degranulation. Taken together, we find that liver palmitate not only supports tumour intrinsic processes but also enables immune evasion.</p>

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Palmitate promotes liver metastases by decreasing neutrophil antitumour behaviour

  • 期刊论文

  • 发表日期：

    2026年8月5日

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  • Anke Vandekeere,
  • Juan Fernández-García,
  • Yiming Peng-Winkler,
  • Miguel Martín Pérez,
  • Ming Liu,
  • Sara Isabel Fernandes,
  • Janine Theile,
  • Philipp Willnow,
  • Sanne Verheul,
  • Gitte Zels,
  • Anirudh Pabba,
  • Christine Desmedt,
  • Cornelis Verhoef,
  • Patricia Altea-Manzano,
  • Salvador Aznar Benitah,
  • Ilaria Elia,
  • Ilaria Malanchi,
  • Sarah-Maria Fendt

摘要

Liver metastases are frequent and challenging to treat owing to the liver’s metabolically active and immune-tolerant environment. However, how cancer cells exploit nutrient availability in the liver to evade immune surveillance remains unknown. Here we show that cancer cells use the palmitate availability in the liver to impair the neutrophil antitumour function. Mechanistically, we find that breast and colorectal cancer cells metastasizing to the liver, but not the lung, require the palmitoyltransferase 17 (DHHC17, gene name ZDHHC17) to stabilize laminin-511 enabling its secretion. In turn, neutrophils in the liver metastasis environment respond to laminin-511 by decreasing their cancer cell-killing capacity. Consistently, silencing ZDHHC17 in cancer cells decreases liver metastases only in the presence of neutrophils, while metastasis growth is restored in ZDHHC17-silenced metastases upon injection of laminin-511 or inhibition of neutrophil degranulation. Taken together, we find that liver palmitate not only supports tumour intrinsic processes but also enables immune evasion.