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

Lucia De Monte, Sonja Wörmann, Emanuela Brunetto, Silvia Heltai, Gilda Magliacane, Michele Reni, Anna Maria Paganoni, Helios Recalde, Anna Mondino, Massimo Falconi, Francesca Aleotti, Gianpaolo Balzano, Hana Algül, Claudio Doglioni, Maria Pia Protti

Research output: Contribution to journalArticle

Abstract

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 pancreatic 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.

Original languageEnglish
Pages (from-to)1792-1803
Number of pages12
JournalCancer Research
Volume76
Issue number7
DOIs
Publication statusPublished - Apr 1 2016

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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