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

doi:10.1158/0008-5472.CAN-15-1801-T

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

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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 language	English
Pages (from-to)	1792-1803
Number of pages	12
Journal	Cancer Research
Volume	76
Issue number	7
DOIs	https://doi.org/10.1158/0008-5472.CAN-15-1801-T
State	Published - 1 Apr 2016
Externally published	Yes

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De Monte, L., Wörmann, S., Brunetto, E., Heltai, S., Magliacane, G., Reni, M., Paganoni, A. M., Recalde, H., Mondino, A., Falconi, M., Aleotti, F., Balzano, G., Algül, H., Doglioni, C., & Protti, M. P. (2016). Basophil recruitment into tumor-draining lymph nodes correlates with Th2 inflammation and reduced survival in pancreatic cancer patients. Cancer Research, 76(7), 1792-1803. https://doi.org/10.1158/0008-5472.CAN-15-1801-T

@article{acedf3ad3ce64607a720394138f344bc,

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}",

note = "Publisher Copyright: {\textcopyright} 2016 AACR. {\textcopyright} 2016 American Association for Cancer Research.",

year = "2016",

month = apr,

day = "1",

doi = "10.1158/0008-5472.CAN-15-1801-T",

language = "English",

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pages = "1792--1803",

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De Monte, L, Wörmann, S, Brunetto, E, Heltai, S, Magliacane, G, Reni, M, Paganoni, AM, Recalde, H, Mondino, A, Falconi, M, Aleotti, F, Balzano, G, Algül, H, Doglioni, C & Protti, MP 2016, 'Basophil recruitment into tumor-draining lymph nodes correlates with Th2 inflammation and reduced survival in pancreatic cancer patients', Cancer Research, vol. 76, no. 7, pp. 1792-1803. https://doi.org/10.1158/0008-5472.CAN-15-1801-T

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.

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

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

M3 - Article

C2 - 26873846

AN - SCOPUS:84963778169

SN - 0008-5472

VL - 76

SP - 1792

EP - 1803

JO - Cancer Research

JF - Cancer Research

IS - 7

ER -

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

Abstract

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