Characterization of the Neuroendocrine Tumor Immune Microenvironment.
Characterization of the Neuroendocrine Tumor Immune Microenvironment.
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DOI：
10.1097/mpa.0000000000001150
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发表时间：
2018-10
期刊：
影响因子：
2.9
通讯作者：
Kulke MH
中科院分区：
文献类型：
--
作者：
da Silva A;Bowden M;Zhang S;Masugi Y;Thorner AR;Herbert ZT;Zhou CW;Brais L;Chan JA;Hodi FS;Rodig S;Ogino S;Kulke MH
免疫环境和神经内分泌肿瘤（NETs）对免疫检查点抑制剂的反应潜力在很大程度上仍未被探索。我们评估了小肠和胰腺神经内分泌肿瘤患者的免疫检查点标志物表达、淋巴细胞浸润和相关突变谱。我们评估了64例小肠（SINET）和31例胰腺神经内分泌肿瘤（pNET）档案组织中PDCD1 （PD-1）、CD274 （PD-L1）和PDCD1LG2 （PD-L2）的表达。我们还评估了T细胞浸润情况，根据T细胞标志物CD3、CD8、CD45RO （PTPRC）或FOXP3的表达对T细胞亚群进行了分类。最后，我们探讨了免疫检查点标志物表达、淋巴细胞浸润和肿瘤突变谱之间的关系。PD-1或PD-L1在小肠或胰腺NET中表达罕见，而PD-L2在两种NET亚型中表达普遍。pNET中t细胞浸润比SINET中多。我们发现在每种肿瘤类型中，免疫检查点标记物表达、免疫浸润和特定突变谱之间没有明确的关联。我们的研究结果为分化良好的神经内分泌肿瘤的免疫环境提供了初步评估。需要进一步研究pNET和SINET之间的免疫学差异，以及PD-L2在这些肿瘤中的作用。
The immune environment and the potential for neuroendocrine tumors (NETs) to respond to immune checkpoint inhibitors remain largely unexplored. We assessed immune checkpoint marker expression, lymphocytic infiltrate, and associated mutational profiles in a cohort of small intestine and pancreatic neuroendocrine tumors. We assessed expression of PDCD1 (PD-1), CD274 (PD-L1) and PDCD1LG2 (PD-L2 ) in archival tissue from 64 small intestine (SINET) and 31 pancreatic neuroendocrine tumors (pNET). We additionally assessed T cell infiltrates, categorizing T cell subsets based on expression of the T cell markers CD3, CD8, CD45RO (PTPRC) or FOXP3. Finally, we explored associations between immune checkpoint marker expression, lymphocytic infiltrate and tumor mutational profiles. Expression of PD-1 or PD-L1 in small intestine or pancreatic NET was rare, while expression of PD-L2 was common in both NET subtypes. T-cell infiltrates were more abundant in pNET than in SINET. We found no clear associations between immune checkpoint marker expression, immune infiltrates, and specific mutational profile within each tumor type. Our findings provide an initial assessment of the immune environment of well-differentiated neuroendocrine tumors. Further studies to define the immunologic differences between pNET and SINET, as well as the role of PD-L2 in these tumors, are warranted.