CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Fibrinogen-like protein 2 in gastrointestinal stromal tumour.
Fibrinogen-like protein 2 in gastrointestinal stromal tumour.
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胃肠道间质瘤(GIST)是胃肠道最常见的肉瘤,可使用伊马替尼等酪氨酸激酶抑制剂有效治疗。癌症免疫疗法对GIST的疗效有限,而人们对GIST中的免疫抑制因子知之甚少。纤维蛋白原样蛋白2(FGL2)既可作为膜相关蛋白表达,也可作为具有免疫抑制功能的可溶性分泌蛋白。
本研究在大型人类癌症转录组数据库中发现,与其他癌症类型相比,GIST的FGL2 mRNA表达较高。两个大型临床系列的免疫组化分析也显示GIST中常见FGL2表达:425例中有333例(78%)FGL2阳性。GIST可能起源于卡哈尔间质细胞,而这些细胞也表达FGL2。FGL2表达与较小的GIST肿瘤体积、较低的有丝分裂计数和较少的TIL(肿瘤浸润淋巴细胞)相关。FGL2阳性GIST患者的无复发生存期优于FGL2阴性患者。伊马替尼可上调GIST细胞系中的FGL2;对于FGL2阴性GIST患者,长期辅助伊马替尼似乎获益最大。研究者据此认为,GIST中常见FGL2表达,且其表达与TIL较少和较好的生存结局相关。
Gastrointestinal stromal tumour (GIST), the most common sarcoma of the gastrointestinal tract, can be treated effectively with tyrosine kinase inhibitors, such as imatinib. Cancer immune therapy has limited efficacy, and little is known about the immune suppressive factors in GISTs. Fibrinogen-like protein 2 (FGL2) is expressed either as a membrane-associated protein or as a secreted soluble protein that has immune suppressive functions.
We found that GISTs expressed FGL2 mRNA highly compared to other types of cancer in a large human cancer transcriptome database. GIST expressed FGL2 frequently also when studied using immunohistochemistry in two large clinical series, where 333 (78%) out of the 425 GISTs were FGL2 positive. The interstitial cells of Cajal, from which GISTs may originate, expressed FGL2.
FGL2 expression was associated with small GIST size, low mitotic counts and low tumour-infiltrating lymphocyte (TIL) counts. Patients whose GIST expressed FGL2 had better recurrence-free survival than patients whose GIST lacked expression. Imatinib upregulated FGL2 in GIST cell lines, and the patients with FGL2-negative GIST appeared to benefit most from long duration of adjuvant imatinib.
We conclude that GISTs express FGL2 frequently and that FGL2 expression is associated with low TIL counts and favourable survival outcomes.
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