Cancer cell, 2012-06, Vol.21 (6), p.822-835
2012
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- Autor(en) / Beteiligte
- Titel
- Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor Regulates Myeloid Inflammation and T Cell Immunity in Pancreatic Cancer
- Ist Teil von
- Cancer cell, 2012-06, Vol.21 (6), p.822-835
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. ► Tumor-derived GM-CSF drives immunosuppressive inflammation in pancreatic carcinoma ► Abrogation of GM-CSF blocks tumor development in a T-cell-dependent fashion ► In humans, PDA tumor cells prominently express GM-CSF in vivo ► Findings suggest a therapeutic mechanism to target inflammation in pancreatic cancer
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1535-6108eISSN: 1878-3686DOI: 10.1016/j.ccr.2012.04.025Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3575028
- Format
- –
- Schlagworte
- Adenocarcinoma - immunology, Adenocarcinoma - metabolism, Adenocarcinoma - pathology, Animals, Carcinoma, Pancreatic Ductal - immunology, Carcinoma, Pancreatic Ductal - metabolism, Carcinoma, Pancreatic Ductal - pathology, CD11b Antigen - immunology, CD11b Antigen - metabolism, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - metabolism, CD8-Positive T-Lymphocytes - pathology, Cell Line, Tumor, Granulocyte-Macrophage Colony-Stimulating Factor - genetics, Granulocyte-Macrophage Colony-Stimulating Factor - immunology, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism, Humans, Immunohistochemistry, Inflammation - immunology, Inflammation - metabolism, Mice, Mice, Knockout, Mice, Transgenic, Models, Immunological, Myeloid Cells - immunology, Myeloid Cells - metabolism, Myeloid Cells - pathology, Pancreatic Neoplasms - immunology, Pancreatic Neoplasms - metabolism, Pancreatic Neoplasms - pathology, Receptors, Chemokine - immunology, Receptors, Chemokine - metabolism, RNA Interference, T-Lymphocytes - immunology, T-Lymphocytes - metabolism, T-Lymphocytes - pathology, Tumor Microenvironment - immunology