Melanoma Cells Inhibit Natural Killer Cell Function by Modulating the Expression of Activating Receptors and Cytolytic Activity

被引：259

作者：

Pietra, Gabriella ^{[2
,3
]}

Manzini, Claudia ^{[2
,3
]}

Rivara, Silvia ^{[2
,3
]}

Vitale, Massimo ^{[4
]}

Cantoni, Claudia ^{[1
,2
,3
]}

Petretto, Andrea ^{[1
]}

Balsamo, Mirna ^{[1
]}

Conte, Romana ^{[4
]}

Benelli, Roberto ^{[4
]}

Minghelli, Simona ^{[5
]}

Solari, Nicola ^{[4
]}

Gualco, Marina ^{[4
]}

Queirolo, Paola ^{[4
]}

Moretta, Lorenzo ^{[1
]}

Mingari, Maria Cristina ^{[2
,3
,4
]}

机构：

[1] Ist Giannina Gaslini, Largo G Gaslini 5, I-16147 Genoa, Italy

[2] Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy

[3] Univ Genoa, Ctr Eccellenza Ric Biomed, Genoa, Italy

[4] IRCCS AOU San Martino IST, Genoa, Italy

[5] Ctr Biotecnol Avanzate, Genoa, Italy

来源：

CANCER RESEARCH | 2012年 / 72卷 / 06期

关键词：

NK CELLS; INDOLEAMINE 2,3-DIOXYGENASE; PROGNOSTIC-SIGNIFICANCE; T-CELLS; NKG2D; CANCER; CYTOTOXICITY; IMMUNOTHERAPY; LIGANDS; DNAM-1;

D O I：

10.1158/0008-5472.CAN-11-2544

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Natural killer (NK) cells play a key role in tumor immune surveillance. However, adoptive immunotherapy protocols using NK cells have shown limited clinical efficacy to date, possibly due to tumor escape mechanisms that inhibit NK cell function. In this study, we analyzed the effect of coculturing melanoma cells and NK cells on their phenotype and function. We found that melanoma cells inhibited the expression of major NK receptors that trigger their immune function, including NKp30, NKp44, and NKG2D, with consequent impairment of NK cell-mediated cytolytic activity against various melanoma cell lines. This inhibitory effect was primarily mediated by indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2). Together, our findings suggest that immunosuppressive barriers erected by tumors greatly hamper the antitumor activity of human NK cells, thereby favoring tumor outgrowth and progression. Cancer Res; 72(6) 1407-15. (C) 2012 AACR,

引用

页码：1407 / 1415

页数：9

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