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Galectin-1促使免疫抑制以及其在肺癌、头颈肿瘤中的作用

2018年11月17日

编译：肿瘤资讯

来源：肿瘤资讯

Galectin-1促使免疫抑制以及其在肺癌、头颈肿瘤中的作用

Quynh-Thu Le

教授

斯坦福大学医学院放疗科主任
斯坦福肿瘤研究所放疗生物研究计划副主任
NRG肿瘤学会头颈肿瘤委员会主席

Quynh教授的研究着重于转化医学。她的课题组是首批发现头颈肿瘤血液循环中缺氧相关分子标志物的团体之一，这些标志物已被用于临床试验，来探索肿瘤缺氧相关治疗策略。在今天的演讲中，她将展示Galectin-1的作用，Galectin-1是一种受缺氧调节的蛋白，在数种癌症中可导致免疫抑制。Galectin-1蛋白由癌细胞分泌，可以杀死T细胞，而T细胞是免疫监控的关键。她和她的研究小组先前已经证明，放疗增强了肿瘤的Galectin-1分泌，导致接受放射治疗的患者循环T细胞数量大幅下降。这些数据提示阻断肿瘤Galectin-1的活性可以防止放疗导致的T细胞耗竭，从而获得更好的放疗治疗效果。过去十年的开创性工作已经确定了我们可以使用免疫检查点抑制剂(ICI)重新激活我们自己的免疫系统来对抗肿瘤。然而，这些抑制剂只对T细胞能进入肿瘤的一小部分患者有效。癌细胞为了阻止T细胞进入，设置了几种屏障。她表明Galectin-1就是其中一个障碍。阻断Galectin-1可以使更多的T细胞穿过血管内皮细胞、进入肿瘤并识别更多的癌细胞。机制上，Galectin-1改变肿瘤内皮细胞的蛋白表达，上调细胞表面PD-L1和Galectin-9。抑制Galectin-1能增加肿瘤内T细胞浸润，使抗PD1治疗+/-放疗有更好的治疗效果。此外，肿瘤Galectin-1水平与免疫检查点抑制剂治疗的头颈肿瘤患者的存活率呈负相关。她的研究揭示了Galectin-1在将肿瘤血管内皮细胞转化为免疫抑制屏障的新功能，抑制Galectin-1可以与免疫检查点抑制剂协同作用。

The role of Galectin-1 in driving immune suppression in lung and head and neck cancers

Professor Quynh’s research focuses on translating laboratory findings to the clinic and vice versa in head and neck cancer (HNC), specifically in the area of tumor hypoxia. Hers was one of the first groups that identified circulating biomarkers for tumor hypoxia in HNC, leading to the application of some of these markers in clinical trials, testing hypoxia targeted strategies. In today’s presentation, she will demonstrate the role of Galectin-1, which is a hypoxia-regulated protein, in driving immune suppression in several cancers. Galectin-1 protein, which is secreted by cancer cells and can kill T cells, which are the crucial for immune surveillance. She and her group have previously shown that the tumor secretion of Galectin-1 is enhanced by radiation, resulting in a substantial decline in the number of circulating T cells in patients receiving radiotherapy. These data suggest that blocking the activity of tumor Galectin-1 can prevent T cell depletion from radiation, thereby leading to better treatment outcomes with radiotherapy. Pioneering work in the last decade have identified means by which we could reactivate our own immune system against tumor through the immune checkpoint inhibitors (ICI). However, these inhibitors work only in a small subset of patients whose T cells can enter the tumor. There are several barriers set up by cancer cells to prevent T cell from getting to them. She shows that Galectin-1 is one of such barriers. Blocking Galectin-1 allows more T cells to penetrate tumors from the vasculature and recognize more cancer cells. Mechanistically, Galectin-1 reprograms the tumor endothelium to upregulate cell-surface PD-L1 and Galectin-9. Galectin-1 blockade increases intra-tumoral T cell infiltration, leading to better response to anti-PD1 therapy +/- radiotherapy. Moreover, tumor Galectin-1 level inversely correlates with survival in head and neck cancer patients treated with ICI. Her study reveals a novel Galectin-1’s function in transforming tumor endothelium into an immune-suppressive barrier and that its inhibition synergizes with immune checkpoint inhibitors.