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

Authors

  • Paola Vacca,

    1. Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy
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    • These authors contributed equally to this work.

  • Stefania Martini,

    1. IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy
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    • These authors contributed equally to this work.

  • Valentina Garelli,

    1. IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy
    2. DiMI Department of Internal Medicine, University of Genova, Genova, Italy
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  • Giovanni Passalacqua,

    1. IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy
    2. DiMI Department of Internal Medicine, University of Genova, Genova, Italy
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  • Lorenzo Moretta,

    Corresponding author
    1. Giannina Gaslini Institute, Genova, Italy
    • Full correspondence: Prof. Lorenzo Moretta, Giannina Gaslini Institute, L.go Gerolamo Gaslini 5, 16147 Genova, Italy

      Fax: +39-010-3730671

      e-mail: lorenzomoretta@ospedale-gaslini.ge.it

      See accompanying Commentary by Tartour and Fridman

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  • Maria Cristina Mingari

    1. Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy
    2. IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy
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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.

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