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

30 Citations (Scopus)

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

Fingerprint

Basophils
Pancreatic Neoplasms
Lymph Nodes
Inflammation
Survival
Adenocarcinoma
Interleukin-4
Neoplasms
Th2 Cells
Chemokine CCL7
Th1 Cells
Tumor Microenvironment
Monocytes
Biomarkers
T-Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Basophil recruitment into tumor-draining lymph nodes correlates with Th2 inflammation and reduced survival in pancreatic cancer patients. / De Monte, Lucia; Wörmann, Sonja; Brunetto, Emanuela; Heltai, Silvia; Magliacane, Gilda; Reni, Michele; Paganoni, Anna Maria; Recalde, Helios; Mondino, Anna; Falconi, Massimo; Aleotti, Francesca; Balzano, Gianpaolo; Algül, Hana; Doglioni, Claudio; Protti, Maria Pia.

In: Cancer Research, Vol. 76, No. 7, 01.04.2016, p. 1792-1803.

Research output: Contribution to journalArticle

De Monte, Lucia ; Wörmann, Sonja ; Brunetto, Emanuela ; Heltai, Silvia ; Magliacane, Gilda ; Reni, Michele ; Paganoni, Anna Maria ; Recalde, Helios ; Mondino, Anna ; Falconi, Massimo ; Aleotti, Francesca ; Balzano, Gianpaolo ; Algül, Hana ; Doglioni, Claudio ; Protti, Maria Pia. / Basophil recruitment into tumor-draining lymph nodes correlates with Th2 inflammation and reduced survival in pancreatic cancer patients. In: Cancer Research. 2016 ; Vol. 76, No. 7. pp. 1792-1803.
@article{0ac3ebbaad0b4bc7926ad0fce80fa424,
title = "Basophil recruitment into tumor-draining lymph nodes correlates with Th2 inflammation and reduced survival in pancreatic cancer patients",
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.",
author = "{De Monte}, Lucia and Sonja W{\"o}rmann and Emanuela Brunetto and Silvia Heltai and Gilda Magliacane and Michele Reni and Paganoni, {Anna Maria} and Helios Recalde and Anna Mondino and Massimo Falconi and Francesca Aleotti and Gianpaolo Balzano and Hana Alg{\"u}l and Claudio Doglioni and Protti, {Maria Pia}",
year = "2016",
month = "4",
day = "1",
doi = "10.1158/0008-5472.CAN-15-1801-T",
language = "English",
volume = "76",
pages = "1792--1803",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

TY - JOUR

T1 - Basophil recruitment into tumor-draining lymph nodes correlates with Th2 inflammation and reduced survival in pancreatic cancer patients

AU - De Monte, Lucia

AU - Wörmann, Sonja

AU - Brunetto, Emanuela

AU - Heltai, Silvia

AU - Magliacane, Gilda

AU - Reni, Michele

AU - Paganoni, Anna Maria

AU - Recalde, Helios

AU - Mondino, Anna

AU - Falconi, Massimo

AU - Aleotti, Francesca

AU - Balzano, Gianpaolo

AU - Algül, Hana

AU - Doglioni, Claudio

AU - Protti, Maria Pia

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84963778169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963778169&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-15-1801-T

DO - 10.1158/0008-5472.CAN-15-1801-T

M3 - Article

AN - SCOPUS:84963778169

VL - 76

SP - 1792

EP - 1803

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 7

ER -