Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic Polarization.
Natural Killer Cells from Malignant Pleural Effusion Are Endowed with a Decidual-Like Proangiogenic Polarization.
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DOI：
10.1155/2018/2438598
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发表时间：
2018
影响因子：
4.1
通讯作者：
Bruno A
中科院分区：
文献类型：
--
作者：
Bosi A;Zanellato S;Bassani B;Albini A;Musco A;Cattoni M;Desio M;Nardecchia E;D'Urso DG;Imperatori A;Dominioni L;Noonan DM;Mortara L;Bruno A
自然杀伤（NK）细胞在肿瘤识别和根除中至关重要，但它们的活性在癌症患者中受损，细胞毒性变差。来自蜕膜的一种特殊类型的NK细胞具有低细胞毒性并显示促血管生成功能。我们研究了患者外周血（PB）和胸腔积液中的NK细胞是否会产生蜕膜样NK表型，以及暴露于IL-2是否可以在胸腔积液中恢复其杀伤能力。来自炎症性疾病（iPE，n = 18）、原发性肿瘤（ptPE，n = 18）和转移性肿瘤（tmPE，n = 27）患者胸腔积液的NK细胞获得了CD 56 brightCD 16 −表型。来自ptPE和tmPE的NK细胞均显示出CD 49 a和CD 69蜕膜样（dNK）标志物的表达增加以及CD 57成熟标志物的水平降低。来自所有分析的PE的NK显示出受损的脱粒能力和减少的穿孔素释放。PE-NK细胞在体外对IL-2刺激有效应答。在培养基中向IL-2中加入TGFβ或无细胞胸水，甚至在健康供体（n = 14）NK中也消除了NK细胞CD 107 a和IFNγ的表达。我们发现tmPE-NK细胞产生VEGF并支持内皮细胞中毛细血管样结构的形成。我们的研究结果表明，PE肿瘤微环境可以将NK细胞极化形成低细胞毒性、蜕膜样、高度促血管生成的表型，而IL-2治疗不足以限制这一过程。
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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通过确定因子的混合物将外周血 NK 细胞转化为蜕膜 NK 样表型。
DOI：
10.4049/jimmunol.1202582
发表时间：
2013-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cerdeira AS;Rajakumar A;Royle CM;Lo A;Husain Z;Thadhani RI;Sukhatme VP;Karumanchi SA;Kopcow HD
通讯作者：
Kopcow HD
影响因子：
4.4
作者：
Carrega, Paolo;Bonaccorsi, Irene;Ferlazzo, Guido
通讯作者：
Ferlazzo, Guido
影响因子：
4.8
作者：
Bruno, Antonino;Focaccetti, Chiara;Noonan, Douglas M.
通讯作者：
Noonan, Douglas M.
影响因子：
4
作者：
Chaouat, Gerard;Ledee-Bataille, Nathalie;Dubanchet, Sylvie
通讯作者：
Dubanchet, Sylvie
影响因子：
5.4
作者：
Allan, David S. J.;Rybalov, Basya;Awong, Geneve;Zuniga-Pfluecker, Juan Carlos;Kopcow, Hernan D.;Carlyle, James R.;Strominger, Jack L.
通讯作者：
Strominger, Jack L.