Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients
Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients
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DOI：
10.1158/0008-5472.can-15-1801-t
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发表时间：
2016-04-01
期刊：
影响因子：
11.2
通讯作者：
Protti, Maria Pia
中科院分区：
文献类型：
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作者：
De Monte, Lucia;Wormann, Sonja;Protti, Maria Pia
在胰腺导管腺癌 (PDAC) 中，主要由 Th2 细胞组成的淋巴浸润预示着患者的生存结果不佳。在这种情况下，IL4 信号传导被认为可以稳定 Th2 表型，但 PDAC 中 IL4 的细胞来源尚不清楚。在这里，我们发现表达 IL4 的嗜碱性粒细胞在 PDAC 患者的肿瘤引流淋巴结 (TDLN) 中富集。 TDLN 中存在的嗜碱性粒细胞与肿瘤中的 Th2/Th1 细胞比率显着相关，它们可作为患者术后生存的独立预后生物标志物。对胰腺癌小鼠模型的研究证实了嗜碱性粒细胞在肿瘤进展过程中的功能作用。嗜碱性粒细胞募集到 TDLN 部分依赖于“交替激活”单核细胞释放趋化因子 CCL7/MCP3，而嗜碱性粒细胞激活则由 T 细胞衍生的 IL3 诱导。我们的结果表明，在肿瘤微环境的影响下，TDLN 中嗜碱性粒细胞的募集和激活如何调节 PDAC 中促肿瘤的 Th2 炎症，有助于阐明胰腺癌免疫环境的关键要素。
In pancreatic ductal adenocarcinomas (PDAC), lymphoid infiltrates, comprised mainly of Th2 cells, predict a poor survival outcome in patients. IL4 signaling has been suggested to stabilize the Th2 phenotype in this setting, but the cellular source of IL4 in PDAC is unclear. Here, we show that basophils expressing IL4 are enriched in tumor-draining lymph nodes (TDLN) of PDAC patients. Basophils present in TDLNs correlated significantly with the Th2/Th1 cell ratio in tumors, where they served as an independent prognostic biomarker of patient survival after surgery. Investigations in mouse models of pan-creatic cancer confirmed a functional role for basophils during tumor progression. The recruitment of basophils into TDLN relied partly upon the release of chemokine CCL7/MCP3 by "alternatively activated" monocytes, whereas basophil activation was induced by T-cell-derived IL3. Our results show how basophils recruited and activated in TDLNs under the influence of the tumor microenvironment regulate tumor-promoting Th2 inflammation in PDAC, helping in illuminating a key element of the immune milieu of pancreatic cancer.