Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Cancer Cell. 2012 Jun 12;21(6):822-35. doi: 10.1016/j.ccr.2012.04.025.
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.
癌症相关炎症被认为是免疫监视的障碍，特别是在胰腺导管腺癌（PDA）中。Gr-1(+) CD11b(+) 细胞是 PDA 中癌症炎症的一个关键特征，但仍知之甚少。使用 PDA 的基因工程小鼠模型，我们表明肿瘤衍生的粒细胞-巨噬细胞集落刺激因子（GM-CSF）是驱动 Gr-1(+) CD11b(+) 细胞发展所必需且充分的，这些细胞抑制了抗原特异性 T 细胞。在体内，阻断肿瘤衍生的 GM-CSF 抑制了 Gr-1(+) CD11b(+) 细胞向肿瘤微环境的募集并阻断了肿瘤的发展-这一发现依赖于 CD8(+) T 细胞。在人类中，PDA 肿瘤细胞在体内显著表达 GM-CSF。因此，肿瘤衍生的 GM-CSF 是肿瘤微环境中炎症和免疫抑制的重要调节剂。
