NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong antitumor activity on short-term IL-2 activation

Paola Vacca, Stefania Martini, Valentina Garelli, Giovanni Passalacqua, Lorenzo Moretta, Maria Cristina Mingari

Research output: Contribution to journalArticle

Abstract

NK cells are a major component of innate immunity and exert a potent antitumor effect both in vitro and in vivo. However, NK cells infiltrating solid tumors have been shown to display severely impaired functional capabilities. In this study, we analyzed NK cells present in pleural effusions (PEs) of patients with primary or metastatic tumors of different origin, including mesothelioma and lung, breast, colon, gastric, bladder, and uterus carcinoma. In all instances, freshly isolated PE-NK cells displayed a CD56bright phenotype and expressed normal levels of both activating receptors and HLA class I-specific inhibitory receptors. In addition, they rapidly released large amounts of IFN-γ and TNF-α after stimulation. Upon culture in IL-2, they acquired a potent cytolytic activity against both allogeneic and autologous tumor cells. Tumor cell lysis was primarily mediated by NKG2D and NKp30 and partially by NKp46 and DNAM-1, in agreement with the expression of the corresponding ligands on tumor cells. The finding that PE-NK cells are not functionally impaired and that they can efficiently kill tumor cells upon short-term IL-2 activation may offer important clues for the development of novel approaches in tumor immunotherapy.

Original languageEnglish
Pages (from-to)550-561
Number of pages12
JournalEuropean Journal of Immunology
Volume43
Issue number2
DOIs
Publication statusPublished - Feb 2013

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Keywords

  • Cancer
  • Immune response
  • Immunotherapy
  • NK cells
  • Tumor immunology

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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