Palmitate promotes liver metastases by decreasing neutrophil antitumour behaviour
Menée à l'aide de lignées cellulaires, de modèles murins et d'échantillons de tumeurs primitives ou de métastases hépatiques provenant de personnes atteintes d'un cancer colorectal ou d'un cancer du sein, cette étude met en évidence un mécanisme par lequel l'abondance de palmitate favorise le développement de métastases hépatiques en réduisant les propriétés antitumorales des neutrophiles via la stabilisation de la laminine-511 par la palmitoyltransférase 17 et la sécrétion de cette laminine par les cellules cancéreuses
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.
Nature Metabolism , article en libre accès, 2026