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. Cancer Res; 76(7); 1792-803. ©2016 AACR.
authors.affiliation: Tumor Immunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele Scientific Institute, Milan, Italy. Division of Immunology, Transplantation and Infectious Diseases, IRCCS, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: De Monte
authors.affiliation: Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Wörmann
authors.affiliation: Tumor Immunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele Scientific Institute, Milan, Italy. Division of Immunology, Transplantation and Infectious Diseases, IRCCS, San Raffaele Scientific Institute, Milan, Italy. San Raffaele Vita-Salute University, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Brunetto
authors.affiliation: Tumor Immunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele Scientific Institute, Milan, Italy. Division of Immunology, Transplantation and Infectious Diseases, IRCCS, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Heltai
authors.affiliation: Pathology Unit, IRCCS, San Raffaele Hospital, Milan, Italy. Division of Experimental Oncology, IRCCS, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Gilda
authors.initials: G
authors.lastname: Magliacane
authors.affiliation: Division of Experimental Oncology, IRCCS, San Raffaele Scientific Institute, Milan, Italy. Medical Oncology Department, IRCCS, San Raffaele Hospital, Milan, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.affiliation: Laboratory for Modeling and Scientific Computing (MOX), Dipartimento di Matematica, Politecnico di Milano, Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Paganoni
authors.affiliation: Hematology, Ospedale San Matteo, Pavia, Italy.
authors.forename: Helios
authors.initials: H
authors.lastname: Recalde
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS, San Raffaele Scientific Institute, Milan, Italy. Lymphocyte Activation Unit, IRCCS, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Mondino
authors.affiliation: San Raffaele Vita-Salute University, Milan, Italy. Division of Experimental Oncology, IRCCS, San Raffaele Scientific Institute, Milan, Italy. Pancreatic Surgery Unit, IRCCS, San Raffaele Hospital, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Falconi
authors.affiliation: Division of Experimental Oncology, IRCCS, San Raffaele Scientific Institute, Milan, Italy. Pancreatic Surgery Unit, IRCCS, San Raffaele Hospital, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Aleotti
authors.affiliation: Division of Experimental Oncology, IRCCS, San Raffaele Scientific Institute, Milan, Italy. Pancreatic Surgery Unit, IRCCS, San Raffaele Hospital, Milan, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Balzano
authors.affiliation: Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Hana
authors.initials: H
authors.lastname: Algül
authors.affiliation: San Raffaele Vita-Salute University, Milan, Italy. Pathology Unit, IRCCS, San Raffaele Hospital, Milan, Italy. Division of Experimental Oncology, IRCCS, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.affiliation: Tumor Immunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele Scientific Institute, Milan, Italy. Division of Immunology, Transplantation and Infectious Diseases, IRCCS, San Raffaele Scientific Institute, Milan, Italy. m.protti@hsr.it.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Protti
mesh_terms: D000368:Aged; D001491:Basophils / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D018418:Th2 Cells / Q000276:immunology*