Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity

Gabriella Pietra, Claudia Manzini, Silvia Rivara, Massimo Vitale, Claudia Cantoni, Andrea Petretto, Mirna Balsamo, Romana Conte, Roberto Benelli, Simona Minghelli, Nicola Solari, Marina Gualco, Paola Queirolo, Lorenzo Moretta, Maria Cristina Mingari

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1407-1415
Number of pages9
JournalCancer Research
Volume72
Issue number6
DOIs
Publication statusPublished - Mar 15 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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