Presence of innate lymphoid cells in pleural effusions of primary and metastatic tumors: Functional analysis and expression of PD-1 receptor

Nicola Tumino, Stefania Martini, Enrico Munari, Francesca Scordamaglia, Francesca Besi, Francesca Romana Mariotti, Giuseppe Bogina, Maria Cristina Mingari, Paola Vacca, Lorenzo Moretta

Research output: Contribution to journalArticle

Abstract

The tumor microenvironment (TM) contains a wide variety of cell types and soluble factors capable of suppressing immune responses. While the presence of NK cells in pleural effusions (PE) has been documented, no information exists on the presence of other innate lymphoid cell (ILC) subsets and on the expression of programmed cell death-1 (PD-1) in NK and ILC. The presence of ILC was assessed in PE of 54 patients (n = 33 with mesothelioma, n = 15 with adenocarcinoma and n = 6 with inflammatory pleural diseases) by cell staining with suitable antibody combinations and cytofluorimetric analysis. The cytokine production of ILC isolated from both PE and autologous peripheral blood was analyzed upon cell stimulation and intracytoplasmic staining. We show that, in addition to NK cells, also ILC1, ILC2 and ILC3 are present in malignant PE and that the prevalent subset is ILC3. PE-ILC subsets produced their typical sets of cytokines upon activation. In addition, we analyzed the PD-1 expression on NK/ILC by multiparametric flow-cytometric analysis, while the expression of PD-1 ligand (PD-L1) was evaluated by immunohistochemical analysis. Both NK cells and ILC3 expressed functional PD-1, moreover, both tumor samples and malignant PE-derived tumor cell lines were PD-L1+ suggesting that the interaction between PD-1+ ILC and PD-L1+ tumor cells may hamper antitumor immune responses mediated by NK and ILC.

Original languageEnglish
JournalInternational Journal of Cancer
DOIs
Publication statusE-pub ahead of print - Mar 11 2019

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Programmed Cell Death 1 Receptor
Pleural Effusion
Lymphocytes
Cell Death
Neoplasms
Natural Killer Cells
Malignant Pleural Effusion
Pleural Diseases
Staining and Labeling
Cytokines
Tumor Microenvironment
Mesothelioma
Tumor Cell Line
Adenocarcinoma

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Presence of innate lymphoid cells in pleural effusions of primary and metastatic tumors : Functional analysis and expression of PD-1 receptor. / Tumino, Nicola; Martini, Stefania; Munari, Enrico; Scordamaglia, Francesca; Besi, Francesca; Mariotti, Francesca Romana; Bogina, Giuseppe; Mingari, Maria Cristina; Vacca, Paola; Moretta, Lorenzo.

In: International Journal of Cancer, 11.03.2019.

Research output: Contribution to journalArticle

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abstract = "The tumor microenvironment (TM) contains a wide variety of cell types and soluble factors capable of suppressing immune responses. While the presence of NK cells in pleural effusions (PE) has been documented, no information exists on the presence of other innate lymphoid cell (ILC) subsets and on the expression of programmed cell death-1 (PD-1) in NK and ILC. The presence of ILC was assessed in PE of 54 patients (n = 33 with mesothelioma, n = 15 with adenocarcinoma and n = 6 with inflammatory pleural diseases) by cell staining with suitable antibody combinations and cytofluorimetric analysis. The cytokine production of ILC isolated from both PE and autologous peripheral blood was analyzed upon cell stimulation and intracytoplasmic staining. We show that, in addition to NK cells, also ILC1, ILC2 and ILC3 are present in malignant PE and that the prevalent subset is ILC3. PE-ILC subsets produced their typical sets of cytokines upon activation. In addition, we analyzed the PD-1 expression on NK/ILC by multiparametric flow-cytometric analysis, while the expression of PD-1 ligand (PD-L1) was evaluated by immunohistochemical analysis. Both NK cells and ILC3 expressed functional PD-1, moreover, both tumor samples and malignant PE-derived tumor cell lines were PD-L1+ suggesting that the interaction between PD-1+ ILC and PD-L1+ tumor cells may hamper antitumor immune responses mediated by NK and ILC.",
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T2 - Functional analysis and expression of PD-1 receptor

AU - Tumino, Nicola

AU - Martini, Stefania

AU - Munari, Enrico

AU - Scordamaglia, Francesca

AU - Besi, Francesca

AU - Mariotti, Francesca Romana

AU - Bogina, Giuseppe

AU - Mingari, Maria Cristina

AU - Vacca, Paola

AU - Moretta, Lorenzo

N1 - © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

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N2 - The tumor microenvironment (TM) contains a wide variety of cell types and soluble factors capable of suppressing immune responses. While the presence of NK cells in pleural effusions (PE) has been documented, no information exists on the presence of other innate lymphoid cell (ILC) subsets and on the expression of programmed cell death-1 (PD-1) in NK and ILC. The presence of ILC was assessed in PE of 54 patients (n = 33 with mesothelioma, n = 15 with adenocarcinoma and n = 6 with inflammatory pleural diseases) by cell staining with suitable antibody combinations and cytofluorimetric analysis. The cytokine production of ILC isolated from both PE and autologous peripheral blood was analyzed upon cell stimulation and intracytoplasmic staining. We show that, in addition to NK cells, also ILC1, ILC2 and ILC3 are present in malignant PE and that the prevalent subset is ILC3. PE-ILC subsets produced their typical sets of cytokines upon activation. In addition, we analyzed the PD-1 expression on NK/ILC by multiparametric flow-cytometric analysis, while the expression of PD-1 ligand (PD-L1) was evaluated by immunohistochemical analysis. Both NK cells and ILC3 expressed functional PD-1, moreover, both tumor samples and malignant PE-derived tumor cell lines were PD-L1+ suggesting that the interaction between PD-1+ ILC and PD-L1+ tumor cells may hamper antitumor immune responses mediated by NK and ILC.

AB - The tumor microenvironment (TM) contains a wide variety of cell types and soluble factors capable of suppressing immune responses. While the presence of NK cells in pleural effusions (PE) has been documented, no information exists on the presence of other innate lymphoid cell (ILC) subsets and on the expression of programmed cell death-1 (PD-1) in NK and ILC. The presence of ILC was assessed in PE of 54 patients (n = 33 with mesothelioma, n = 15 with adenocarcinoma and n = 6 with inflammatory pleural diseases) by cell staining with suitable antibody combinations and cytofluorimetric analysis. The cytokine production of ILC isolated from both PE and autologous peripheral blood was analyzed upon cell stimulation and intracytoplasmic staining. We show that, in addition to NK cells, also ILC1, ILC2 and ILC3 are present in malignant PE and that the prevalent subset is ILC3. PE-ILC subsets produced their typical sets of cytokines upon activation. In addition, we analyzed the PD-1 expression on NK/ILC by multiparametric flow-cytometric analysis, while the expression of PD-1 ligand (PD-L1) was evaluated by immunohistochemical analysis. Both NK cells and ILC3 expressed functional PD-1, moreover, both tumor samples and malignant PE-derived tumor cell lines were PD-L1+ suggesting that the interaction between PD-1+ ILC and PD-L1+ tumor cells may hamper antitumor immune responses mediated by NK and ILC.

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