Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic Polarization

Natural killer (NK) cells are crucial in tumor recognition and eradication, but their activity is impaired in cancer patients, becoming poorly cytotoxic. A particular type of NK cells, from the decidua, has low cytotoxicity and shows proangiogenic functions. We investigated whether NK cells from per...

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Main Authors: Annalisa Bosi, Silvia Zanellato, Barbara Bassani, Adriana Albini, Alessandra Musco, Maria Cattoni, Matteo Desio, Elisa Nardecchia, Davide Giuseppe D’Urso, Andrea Imperatori, Lorenzo Dominioni, Douglas M. Noonan, Lorenzo Mortara, Antonino Bruno
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2018/2438598
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author Annalisa Bosi
Silvia Zanellato
Barbara Bassani
Adriana Albini
Alessandra Musco
Maria Cattoni
Matteo Desio
Elisa Nardecchia
Davide Giuseppe D’Urso
Andrea Imperatori
Lorenzo Dominioni
Douglas M. Noonan
Lorenzo Mortara
Antonino Bruno
author_facet Annalisa Bosi
Silvia Zanellato
Barbara Bassani
Adriana Albini
Alessandra Musco
Maria Cattoni
Matteo Desio
Elisa Nardecchia
Davide Giuseppe D’Urso
Andrea Imperatori
Lorenzo Dominioni
Douglas M. Noonan
Lorenzo Mortara
Antonino Bruno
author_sort Annalisa Bosi
collection DOAJ
description Natural killer (NK) cells are crucial in tumor recognition and eradication, but their activity is impaired in cancer patients, becoming poorly cytotoxic. A particular type of NK cells, from the decidua, has low cytotoxicity and shows proangiogenic functions. We investigated whether NK cells from peripheral blood (PB) and pleural effusions of patients develop decidual-like NK phenotype and whether exposure to IL-2 can restore their killing ability in the presence of pleural fluids. NK cells from pleural effusion of patients with inflammatory conditions (iPE, n = 18), primary tumor (ptPE, n = 18), and metastatic tumor (tmPE, n = 27) acquired the CD56brightCD16− phenotype. NK cells from both ptPE and tmPE showed increased expression for the CD49a and CD69 decidual-like (dNK) markers and decreased levels of the CD57 maturation marker. NK from all the PE analyzed showed impaired degranulation capability and reduced perforin release. PE-NK cells efficiently responded to IL-2 stimulation in vitro. Addition of TGFβ or cell-free pleural fluid to IL-2 in the culture medium abrogated NK cell CD107a and IFNγ expression even in healthy donors (n = 14) NK. We found that tmPE-NK cells produce VEGF and support the formation of capillary-like structures in endothelial cells. Our results suggest that the PE tumor microenvironment can shape NK cell polarization towards a low cytotoxic, decidual-like, highly proangiogenic phenotype and that IL-2 treatment is not sufficient to limit this process.
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spelling doaj-art-8bfaba409b824cf9a32ecda0c698ff1d2025-02-03T06:42:24ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/24385982438598Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic PolarizationAnnalisa Bosi0Silvia Zanellato1Barbara Bassani2Adriana Albini3Alessandra Musco4Maria Cattoni5Matteo Desio6Elisa Nardecchia7Davide Giuseppe D’Urso8Andrea Imperatori9Lorenzo Dominioni10Douglas M. Noonan11Lorenzo Mortara12Antonino Bruno13Vascular Biology and Angiogenesis Laboratory, Scientific and Technology Pole, IRCCS MultiMedica, Milano, ItalyImmunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, Varese, ItalyVascular Biology and Angiogenesis Laboratory, Scientific and Technology Pole, IRCCS MultiMedica, Milano, ItalyVascular Biology and Angiogenesis Laboratory, Scientific and Technology Pole, IRCCS MultiMedica, Milano, ItalyImmunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, Varese, ItalyVascular Biology and Angiogenesis Laboratory, Scientific and Technology Pole, IRCCS MultiMedica, Milano, ItalyDepartment of Medicine and Surgery, University of Insubria, Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, Varese, ItalyVascular Biology and Angiogenesis Laboratory, Scientific and Technology Pole, IRCCS MultiMedica, Milano, ItalyImmunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, Varese, ItalyVascular Biology and Angiogenesis Laboratory, Scientific and Technology Pole, IRCCS MultiMedica, Milano, ItalyNatural killer (NK) cells are crucial in tumor recognition and eradication, but their activity is impaired in cancer patients, becoming poorly cytotoxic. A particular type of NK cells, from the decidua, has low cytotoxicity and shows proangiogenic functions. We investigated whether NK cells from peripheral blood (PB) and pleural effusions of patients develop decidual-like NK phenotype and whether exposure to IL-2 can restore their killing ability in the presence of pleural fluids. NK cells from pleural effusion of patients with inflammatory conditions (iPE, n = 18), primary tumor (ptPE, n = 18), and metastatic tumor (tmPE, n = 27) acquired the CD56brightCD16− phenotype. NK cells from both ptPE and tmPE showed increased expression for the CD49a and CD69 decidual-like (dNK) markers and decreased levels of the CD57 maturation marker. NK from all the PE analyzed showed impaired degranulation capability and reduced perforin release. PE-NK cells efficiently responded to IL-2 stimulation in vitro. Addition of TGFβ or cell-free pleural fluid to IL-2 in the culture medium abrogated NK cell CD107a and IFNγ expression even in healthy donors (n = 14) NK. We found that tmPE-NK cells produce VEGF and support the formation of capillary-like structures in endothelial cells. Our results suggest that the PE tumor microenvironment can shape NK cell polarization towards a low cytotoxic, decidual-like, highly proangiogenic phenotype and that IL-2 treatment is not sufficient to limit this process.http://dx.doi.org/10.1155/2018/2438598
spellingShingle Annalisa Bosi
Silvia Zanellato
Barbara Bassani
Adriana Albini
Alessandra Musco
Maria Cattoni
Matteo Desio
Elisa Nardecchia
Davide Giuseppe D’Urso
Andrea Imperatori
Lorenzo Dominioni
Douglas M. Noonan
Lorenzo Mortara
Antonino Bruno
Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic Polarization
Journal of Immunology Research
title Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic Polarization
title_full Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic Polarization
title_fullStr Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic Polarization
title_full_unstemmed Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic Polarization
title_short Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic Polarization
title_sort natural killer cells from malignant pleural effusion are endowed with a decidual like proangiogenic polarization
url http://dx.doi.org/10.1155/2018/2438598
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