GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy.
GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy.
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DOI：
10.1158/0008-5472.can-20-2870
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发表时间：
2021-05-01
期刊：
影响因子：
11.2
通讯作者：
Meylan E
中科院分区：
文献类型：
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作者：
Ancey PB;Contat C;Boivin G;Sabatino S;Pascual J;Zangger N;Perentes JY;Peters S;Abel ED;Kirsch DG;Rathmell JC;Vozenin MC;Meylan E
中性粒细胞是循环中最丰富的白细胞，对先天免疫是必不可少的。在癌症中，促肿瘤或抗肿瘤的特性被归因于肿瘤相关的中性粒细胞(TAN)。在这里，专注于Tan在肺肿瘤中的积累，我们确定Glut1是肿瘤支持行为的必要葡萄糖转运体。与正常的中性粒细胞相比，肺腺癌模型小鼠的TAN中的Glut1和葡萄糖代谢增加。为了阐明葡萄糖摄取对TANS的影响，我们使用了两种重组酶的策略，将肿瘤起始与中性粒细胞特异性Glut1缺失分离开来。Glut1的丢失加速了肿瘤中性粒细胞的更新，并减少了表达SiglecF的TANs亚群。在TANS缺乏Glut1表达的情况下，肿瘤生长减少，放射治疗的疗效增强。我们的结果证明了Glut1在TANS中的重要性，这可能会影响它们的亲肿瘤和抗肿瘤行为。这些结果还表明，将代谢脆弱性作为靶点，有利于抗肿瘤中性粒细胞。
Neutrophils are the most abundant circulating leucocytes and are essential for innate immunity. In cancer, pro- or anti-tumor properties have been attributed to tumor-associated neutrophils (TAN). Here, focusing on TAN accumulation within lung tumors, we identify Glut1 as an essential glucose transporter for their tumor supportive behavior. Compared to normal neutrophils, Glut1 and glucose metabolism increased in TANs from a mouse model of lung adenocarcinoma. To elucidate the impact of glucose uptake on TANs, we used a strategy with two recombinases, dissociating tumor initiation from neutrophil-specific Glut1 deletion. Loss of Glut1 accelerated neutrophil turnover in tumors and reduced a subset of TANs expressing SiglecF. In the absence of Glut1 expression by TANs, tumor growth was diminished and the efficacy of radiotherapy was augmented. Our results demonstrate the importance of Glut1 in TANs, which may affect their pro- versus anti-tumor behavior. These results also suggest targeting metabolic vulnerabilities to favor anti-tumor neutrophils.