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Natural Killer Cells From Malignant Pleural Effusion Are Endowed With A Decidual-Like Proangiogenic Polarization

Annalisa Bosi, Silvia Zanellato, B. Bassani, A. Albini, A. Musco, M. Cattoni, M. Desio, E. Nardecchia, D. D'Urso, A. Imperatori, L. Dominioni, D. Noonan, L. Mortara, A. Bruno
Published 2018 · Medicine, Biology

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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.
This paper references
10.1200/JCO.2014.57.3329
Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer.
K. Conlon (2015)
10.1158/2159-8290.CD-15-0732
STAT5 Is a Key Regulator in NK Cells and Acts as a Molecular Switch from Tumor Surveillance to Tumor Promotion.
D. Gotthardt (2016)
10.1007/s10555-007-9108-5
Inflammation, inflammatory cells and angiogenesis: decisions and indecisions
D. Noonan (2007)
10.1177/1753425912453187
Altered phenotype in peripheral blood and tumor-associated NK cells from colorectal cancer patients
Y. S. Rocca (2013)
10.1200/JCO.2010.30.5037
Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer.
S. Mahmoud (2011)
10.1016/j.jri.2010.11.002
Decidualization and angiogenesis in early pregnancy: unravelling the functions of DC and NK cells.
S. Blois (2011)
10.1038/nri1549
Close encounters of different kinds: Dendritic cells and NK cells take centre stage
M. Degli-Esposti (2005)
10.1111/j.1440-1843.2012.02177.x
Clinical implications of pleural effusions in ovarian cancer
J. M. Porcel (2012)
10.1016/J.YANE.2012.02.046
Hallmarks of Cancer: The Next Generation
M. Roizen (2012)
10.1002/cncr.23239
Natural killer cells infiltrating human nonsmall‐cell lung cancer are enriched in CD56brightCD16− cells and display an impaired capability to kill tumor cells
P. Carrega (2008)
10.1016/J.CDP.2004.04.003
Immunosuppressive mechanisms in the microenvironment of malignant pleural effusions.
J. Sikora (2004)
10.1002/ijc.30289
Impaired T cell function in malignant pleural effusion is caused by TGF‐β derived predominantly from macrophages
L. Li (2016)
10.4049/jimmunol.1202582
Conversion of Peripheral Blood NK Cells to a Decidual NK-like Phenotype by a Cocktail of Defined Factors
Ana T S Cerdeira (2013)
10.1038/nri1936
Cancer despite immunosurveillance: immunoselection and immunosubversion
L. Zitvogel (2006)
10.1002/eji.200939910
TGF‐β affects development and differentiation of human natural killer cell subsets
D. S. Allan (2010)
10.1016/J.JIM.2004.08.008
CD107a as a functional marker for the identification of natural killer cell activity.
G. Alter (2004)
10.1593/NEO.121758
The proangiogenic phenotype of natural killer cells in patients with non-small cell lung cancer.
A. Bruno (2013)
10.1080/2162402X.2015.1115942
Trial Watch—Immunostimulation with cytokines in cancer therapy
E. Vacchelli (2016)
10.1111/j.1600-065X.2008.00651.x
Human NK cells: from HLA class I‐specific killer Ig‐like receptors to the therapy of acute leukemias
A. Moretta (2008)
10.3389/fimmu.2013.00490
The Critical Role of the Tumor Microenvironment in Shaping Natural Killer Cell-Mediated Anti-Tumor Immunity
Joanna Bagińska (2013)
This information is current as Lymph Secondary Lymphoid Organs via Afferent Neoplastic Solid Tissues and Recirculate to NK Cells Are Abundant in Both Healthy and Noncytotoxic HumanlowPerforinbrightCD 56 and
Paolo Carrega (2014)
10.18632/ONCOTARGET.3547
CD163+ tumor-associated macrophage is a prognostic biomarker and is associated with therapeutic effect on malignant pleural effusion of lung cancer patients
L. Yang (2015)
10.3389/fimmu.2015.00482
Critical Role of Tumor Microenvironment in Shaping NK Cell Functions: Implication of Hypoxic Stress
M. Hasmim (2015)
10.1016/j.rmed.2015.05.014
Pleural neoplastic pathology.
G. Karpathiou (2015)
10.1002/ijc.11321
Renal cell carcinoma‐infiltrating natural killer cells express differential repertoires of activating and inhibitory receptors and are inhibited by specific HLA class I allotypes
J. Schleypen (2003)
10.1016/S0065-2776(08)60664-1
Biology of Natural Killer Cells
G. Trinchieri (1989)
10.4161/onci.23638
NK cells from malignant pleural effusions are potent antitumor effectors
P. Vacca (2013)
10.5114/wo.2012.30054
Macrophages in malignant pleural effusions – alternatively activated tumor associated macrophages
Mariusz Kaczmarek (2012)
10.1016/j.jim.2011.07.016
Measurement of NK activity in whole blood by the CD69 up-regulation after co-incubation with K562, comparison with NK cytotoxicity assays and CD107a degranulation assay.
B. Dons’koi (2011)
10.3389/fimmu.2016.00694
STATs in NK-Cells: The Good, the Bad, and the Ugly
D. Gotthardt (2017)
10.1164/rccm.201203-0465PP
Malignant pleural effusion: tumor-host interactions unleashed.
G. Stathopoulos (2012)
Pleural effusion in breast cancer: influence upon clinical course and survival.
T. Singer (1986)
10.1242/jcs.116392
The tumor microenvironment at a glance
F. Balkwill (2012)
Dysregulation of regulatory CD56 NK cells/T cells 16 Journal of Immunology Research interactions in multiple sclerosis
A. Laroni (2016)
10.4049/jimmunol.172.3.1455
The Abundant NK Cells in Human Secondary Lymphoid Tissues Require Activation to Express Killer Cell Ig-Like Receptors and Become Cytolytic1
G. Ferlazzo (2004)
10.1093/jnci/dju200
A Think Tank of TINK/TANKs: Tumor-Infiltrating/Tumor-Associated Natural Killer Cells in Tumor Progression and Angiogenesis
A. Bruno (2014)
CD 56 brightperfor - inlow noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via a ff erent lymph
D. V. Osypchuk (2014)
10.1002/eji.201242783
NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong antitumor activity on short‐term IL‐2 activation
P. Vacca (2013)
10.1186/1479-5876-11-145
Molecular signatures mostly associated with NK cells are predictive of relapse free survival in breast cancer patients
M. Ascierto (2013)
10.1172/JCI45816
Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity.
E. Mamessier (2011)
10.1016/j.imlet.2016.01.007
Human innate lymphoid cells.
E. Montaldo (2016)
10.1016/j.jaut.2016.04.003
Dysregulation of regulatory CD56(bright) NK cells/T cells interactions in multiple sclerosis.
A. Laroni (2016)
10.1111/j.1365-2567.2009.03167.x
Natural killer cells in infection and inflammation of the lung
Fiona J. Culley (2009)
CD 69 is a stimulatory receptor for natural killer cell and its cytotoxic e ff ect is blocked by CD 94 inhibitory receptor Management of the patient with a malignant pleural e ff usion
D. Stefanou G. Karpathiou (2010)
10.1200/JCO.2008.19.6147
In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer.
F. Pagès (2009)
10.3389/fimmu.2013.00422
Functional Significance of CD57 Expression on Human NK Cells and Relevance to Disease
Carolyn M Nielsen (2013)
10.1007/s10555-016-9618-0
Progression and metastasis of lung cancer
H. Popper (2016)
10.1016/j.bbmt.2014.01.006
Preactivation with IL-12, IL-15, and IL-18 induces CD25 and a functional high-affinity IL-2 receptor on human cytokine-induced memory-like natural killer cells.
J. Leong (2014)
10.1111/j.1600-0897.2007.00513.x
Natural Killer (NK) Cells from Killers to Regulators: Distinct Features Between Peripheral Blood and Decidual NK Cells
A. Santoni (2007)
10.1038/nm1452
Decidual NK cells regulate key developmental processes at the human fetal-maternal interface
J. Hanna (2006)
10.4049/jimmunol.1500591
CD56brightCD16− NK Cells Produce Adenosine through a CD38-Mediated Pathway and Act as Regulatory Cells Inhibiting Autologous CD4+ T Cell Proliferation
F. Morandi (2015)
10.1016/j.jtho.2016.06.021
Pleural Effusion of Patients with Malignant Mesothelioma Induces Macrophage‐Mediated T Cell Suppression
L. Lievense (2016)
10.1016/S1471-4906(01)02060-9
The biology of human natural killer-cell subsets.
M. Cooper (2001)
10.1159/000087820
Cytokines and implantation.
G. Chaouat (2005)
10.1016/j.critrevonc.2016.05.004
The Third Italian Consensus Conference for Malignant Pleural Mesothelioma: State of the art and recommendations.
S. Novello (2016)
10.3389/fonc.2014.00131
Orchestration of Angiogenesis by Immune Cells
A. Bruno (2014)
10.1016/j.it.2011.06.013
Origin, phenotype and function of human natural killer cells in pregnancy.
P. Vacca (2011)
10.1055/s-0030-1269831
Management of the patient with a malignant pleural effusion.
J. Heffner (2010)
10.1172/JCI59643
Macrophage plasticity and polarization: in vivo veritas.
A. Sica (2012)
10.1038/ni1582
Functions of natural killer cells
E. Vivier (2008)
10.1016/S1472-6483(10)60796-1
Immune cells in uteroplacental tissues throughout pregnancy: a brief review.
G. Chaouat (2007)
10.1046/j.1365-2567.1999.00738.x
CD69 is a stimulatory receptor for natural killer cell and its cytotoxic effect is blocked by CD94 inhibitory receptor
Borrego (1999)
10.1146/annurev-immunol-020711-075053
Innate lymphoid cells: emerging insights in development, lineage relationships, and function.
H. Spits (2012)
10.1016/J.EJCA.2006.03.022
Role of prostaglandin E2 in the invasiveness, growth and protection of cancer cells in malignant pleuritis.
E. Pace (2006)
10.1007/s00262-015-1701-9
CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion
F. Wang (2015)
10.1126/science.1198687
Innate or Adaptive Immunity? The Example of Natural Killer Cells
E. Vivier (2011)
10.1002/jcp.24806
Review: Cell Dynamics in Malignant Pleural Effusions
E. Giarnieri (2015)
10.1158/0008-5472.CAN-15-1498
IL15 and T-cell Stemness in T-cell-Based Cancer Immunotherapy.
K. Pilipów (2015)
CD 56 brightCD 16 − NK cells produce adenosine through a CD 38 - mediated pathway and act as regulatory cells inhibiting autologous CD 4 + T cell proliferation
M. von Geldern (2015)
10.1073/pnas.0611098104
TGFβ promotes conversion of CD16+ peripheral blood NK cells into CD16− NK cells with similarities to decidual NK cells
D. Keskin (2007)
CD 56 brightperfor - inlow noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via a ff erent lymph
V. P. Chernyshov Dons'koi (2014)



This paper is referenced by
10.1016/j.canlet.2020.09.021
NK cells-directed therapies target circulating tumor cells and metastasis.
Hassan Dianat-Moghadam (2020)
10.3389/fimmu.2019.02587
Innate Immune Response Regulation by the Human RNASET2 Tumor Suppressor Gene
F. Acquati (2019)
10.3390/jcm8091492
NK Cell Plasticity in Cancer
Sizhe Liu (2019)
10.1080/2162402X.2018.1554969
Making cold malignant pleural effusions hot: driving novel immunotherapies
Pranav Murthy (2019)
10.3389/fonc.2019.01366
The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy
G. Chu (2019)
10.3389/fonc.2020.00156
Endometrial Cancer Immune Escape Mechanisms: Let Us Learn From the Fetal–Maternal Interface
V. Bruno (2020)
10.1101/2020.07.06.189449
Prostate cancer peripheral blood NK cells show enhanced CD9, CD49a, CXCR4, CXCL8, MMP-9 production, and secrete monocyte-recruiting and polarizing factors
D. Baci (2020)
10.3390/jcm9010143
Hitting More Birds with a Stone: Impact of TGF-β on ILC Activity in Cancer
C. Fionda (2020)
10.3390/ijms21093125
The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors
D. Baci (2020)
10.3389/fimmu.2019.00771
Myeloid Derived Suppressor Cells Interactions With Natural Killer Cells and Pro-angiogenic Activities: Roles in Tumor Progression
A. Bruno (2019)
10.1165/rcmb.2018-0201OC
IL-17A-Producing γδT Cells Inhibit the Formation of Malignant Pleural Effusions.
Xiaoshan Wei (2019)
10.1016/j.imbio.2020.151910
Trophoblast cell influence on peripheral blood natural killer cell proliferation and phenotype in non-pregnant women and women in early pregnancy.
Valentina A Mikhailova (2020)
10.3390/cancers11040461
Natural Killer Cells as Key Players of Tumor Progression and Angiogenesis: Old and Novel Tools to Divert Their Pro-Tumor Activities into Potent Anti-Tumor Effects
B. Bassani (2019)
10.1158/2326-6066.CIR-18-0757
Accumulation of Tumor-Infiltrating CD49a+ NK Cells Correlates with Poor Prognosis for Human Hepatocellular Carcinoma
H. Sun (2019)
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