Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor Regulates Myeloid Inflammation and T Cell Immunity in Pancreatic Cancer
Menées sur un modèle murin d'adénocarcinome canalaire du pancréas, ces études mettent en évidence le rôle joué par le facteur de croissance des colonies de granulocytes/macrophages dans la régulation de mécanismes inflammatoires et l'échappement à la surveillance immunitaire des tumeurs
Cancer-associated inflammation is thought to be a barrier to immune surveillance, particularly in pancreatic ductal adenocarcinoma (PDA). Gr-1+ CD11b+ cells are a key feature of cancer inflammation in PDA, but remain poorly understood. Using a genetically engineered mouse model of PDA, we show that tumor-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) is necessary and sufficient to drive the development of Gr-1+ CD11b+ cells that suppressed antigen-specific T cells. In vivo, abrogation of tumor-derived GM-CSF inhibited the recruitment of Gr-1+ CD11b+ cells to the tumor microenvironment and blocked tumor development—a finding that was dependent on CD8+ T cells. In humans, PDA tumor cells prominently expressed GM-CSF in vivo. Thus, tumor-derived GM-CSF is an important regulator of inflammation and immune suppression within the tumor microenvironment. º Tumor-derived GM-CSF drives immunosuppressive inflammation in pancreatic carcinoma º Abrogation of GM-CSF blocks tumor development in a T-cell-dependent fashion º In humans, PDA tumor cells prominently express GM-CSF in vivo º Findings suggest a therapeutic mechanism to target inflammation in pancreatic cancer