Basophil recruitment into tumor draining lymph nodes correlates with Th2 inflammation and reduced survival in pancreatic cancer patients

In pancreatic ductal adenocarcinomas (PDAC), lymphoid infiltrates comprised mainly of T helper 2 (Th2) cells predict a poor survival outcome in patients. IL-4 signaling has been suggested to stabilize the Th2 phenotype in this setting, but the cellular source of IL-4 in PDAC is unclear. Here we show that basophils expressing IL-4 are enriched in tumor-draining lymph nodes (TDLNs) 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 pancreatic cancer confirmed a functional role for basophils during tumor progression. 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 IL-3. 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 illuminating a key element of the immune milieu of pancreatic cancer.

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