[PDF][PDF] Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer

LJ Bayne, GL Beatty, N Jhala, CE Clark, AD Rhim… - Cancer cell, 2012 - cell.com
LJ Bayne, GL Beatty, N Jhala, CE Clark, AD Rhim, BZ Stanger, RH Vonderheide
Cancer cell, 2012cell.com
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 …
Summary
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.
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