Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia
By Y. Pylayeva-Gupta, Kyoung Eun Lee, C. Hajdu, G. Miller, D. Bar-Sagi. Cancer Cell, 2012
688 citations recorded by the source corpus.
Summary Stromal responses elicited by early stage neoplastic lesions can promote tumor growth. However, the molecular mechanisms that underlie the early recruitment of stromal cells to sites of neoplasia remain poorly understood. Here we demonstrate an oncogenic KrasG12D-dependent upregulation of GM-CSF in mouse pancreatic ductal epithelial cells (PDEC). An enhanced GM-CSF production is also observed in human PanIN lesions. KrasG12D-dependent production of GM-CSF in vivo is required for the recruitment of Gr1+CD11b+ myeloid cells. The suppression of GM-CSF production inhibits the in vivo growth of KrasG12D-PDECs and, consistent with the role of GM-CSF in Gr1+CD11b+ mobilization, this effect is mediated by CD8+ T cells. These results identify a pathway that links oncogenic activation to the evasion of anti-tumor immunity.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/5ed647dbf5417456b746fbd425ac130a64d36975
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Citations in the corpus
- Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression and improves chemotherapeutic responses (2012, background): “Although TAMs are the most prevalent of these cells, 2 recent reports showed that G-MDSCs mobilized by tumor-derived granulocyte macrophage colony-stimulating factor (GM-CSF) can also suppress CTL activation in PDAC tumors (30, 31).”
- Tumor-derived granulocyte-macrophage colony stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer (2012, result): “Importantly, our results are consistent with data described by Pylayeva-Gupta et al. (Pylayeva-Gupta et al., 2012).”
- New horizons in tumor microenvironment biology: challenges and opportunities (2015, background): “The myeloid-derived suppressor cell (MDSC) population which encompasses immature dendritic cells, neutrophils, monocytes, and early myeloid progenitors implicates tumor-initiated endocrine signaling to the immune system through multiple chemokines such as granulocyte-macrophage colony stimulating fa”
- Tumor cell-intrinsic factors underlie heterogeneity of immune cell infiltration and response to immunotherapy (2018, positive): “We and others have reported that PDA tumor-cell-derived GM-CSF promotes myeloid cell mobilization which suppresses anti-tumor immunity (Bayne et al., 2012; Pylayeva-Gupta et al., 2012).”
- Vitamin D Receptor-Mediated Stromal Reprogramming Suppresses Pancreatitis and Enhances Pancreatic Cancer Therapy (2014, positive): “Of note, stromal VDR activation significantly reduced CSF2 expression, implicated in pancreatic tumor progression and evasion of antitumor immunity (Bayne et al., 2012; Pylayeva-Gupta et al., 2012).”
- CSF1/CSF1R Blockade Reprograms Tumor-Infiltrating Macrophages and Improves Response to T Cell Checkpoint Immunotherapy in Pancreatic Cancer Models (2014, positive): “For example, in response to lipopolysaccharide, CSF2-derived macrophages preferentially produce IL6, IL12, and TNFa, whereas CSF1-derived macrophages produce IL10 and CCL-2, but not IL12.”