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Tumour immunology

Suppressing the rejection of pancreatic tumours

Nature Reviews Immunology volume 12, page 555 (2012)Cite this article

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MDSCs are recruited by KRAS-G12D-transformed pancreatic tumour cells ... to suppress CD8+ T cell-mediated antitumour immune responses

To investigate immunomodulation during the development of PDA, Bayne and colleagues used KPC genetically engineered mice, which have pancreas-specific KrasG12D and Trp53R172H mutations. Pylayeva-Gupta and colleagues used an allograft model in which green fluorescent protein (GFP)+ pancreatic ductal epithelial cells (PDECs) expressing mutant KRAS (KRAS-G12D) were injected into the pancreata of syngeneic mice. Both mouse models developed PanINs and PDAs with features of the human disease. In particular, the tumours in both models were infiltrated by myeloid-derived suppressor cells (MDSCs) — GR1+CD11b+ cells that are thought to suppress T cell-mediated antitumour immune responses. Bayne and colleagues found that MDSCs from KPC mice suppressed T cell proliferation and interferon-γ production in vitro. These authors noted that KPC mice developed splenomegaly as MDSCs and their KIT+ precursors accumulated in the spleen, indicating that a tumour-derived factor might promote the development of MDSCs. Indeed, they found that culturing KIT+ splenocytes isolated from tumour-bearing KPC mice with conditioned media from PDA cells promoted their proliferation and the expression of GR1 and CD11b; these cells suppressed T cell proliferation in vitro.

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ORIGINAL RESEARCH PAPERS

  1. Bayne, L. J. et al. Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 21, 822–835 (2012)

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  2. Pylayeva-Gupta, Y. et al. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell 21, 836–847 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Senior Editor, Nature Reviews Cancer,

    Gemma K. Alderton

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  1. Gemma K. Alderton
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Alderton, G. Suppressing the rejection of pancreatic tumours. Nat Rev Immunol 12, 555 (2012). https://doi.org/10.1038/nri3267

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