Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 43, Issue 2, Pages 550-561Publisher
WILEY
DOI: 10.1002/eji.201242783
Keywords
Cancer; Immune response; Immunotherapy; NK cells; Tumor immunology
Categories
Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [4725]
- Special Program Molecular Clinical Oncology 5x1000 [9962]
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) [RBLA039LSF-001, 20077NFBH8_005, 2008PTB3HC_005]
- Ministero della Salute [RO-strategici 3/07, RFPS-2007-4-633146, strategici 8/07]
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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- and TNF- 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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