Cancer Cell：抑制GM-CSF或成胰腺癌治疗新方法

近日，一项发表在Cancer Cell杂志上的研究论文证实：胰腺癌细胞产生一种蛋白质，吸引人体免疫细胞，帮助癌细胞生长。研究还表明阻断该蛋白可能是一种有效的治疗胰腺癌手段。

胰腺癌（pancreatic carcinoma），是胰脏出现的癌症，其恶性肿瘤会在患者的胰脏生长。通常认为胰腺癌是常见肿瘤中恶性程度最高，也是死亡率最高的。40～70岁多见，男性多于女性。近年来发病率有增高趋势。

研究人员使用胰腺癌小鼠模型发现KRAS突变触发胰腺肿瘤表达一种叫做GM-CSF的蛋白质。他们还发现肿瘤源性GM-CSF聚集在肿瘤组织的不成熟的免疫细胞周围，然后诱导这些细胞变成所谓的髓源性抑制细胞，从而抑制其他免疫细胞，这样胰腺细胞就能逃脱人体的免疫系统，进而生长和分裂。而阻断GM-CSF的产生可以抑制髓源性抑制细胞，恢复免疫系统进而阻止肿瘤的发展。

doi:10.1016/j.ccr.2012.04.025
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Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor Regulates Myeloid Inflammation and T Cell Immunity in Pancreatic Cancer

Lauren J. Bayne, Gregory L. Beatty, Nirag Jhala, Carolyn E. Clark, Andrew D. Rhim, Ben Z. Stanger, Robert H. Vonderheide, et al.

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 developmenta 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.