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Cancer Cell. 2012 Jun 12;21(6):822-35. doi: 10.1016/j.ccr.2012.04.025.

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

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1
Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Abstract

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.

PMID:
22698406
PMCID:
PMC3575028
DOI:
10.1016/j.ccr.2012.04.025
[Indexed for MEDLINE]
Free PMC Article
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