Purpose: Natural Killer (NKs) cells are crucial effector cells of innate immunity able to kill tumor or virus-infected cells. However, in tumor-bearing host the anti-tumor function of NKs are largely impaired. Interestingly, in the early phase of pregnancy, a leading role of a NK cell subset (decidual NKs) with a potent pro-angiogenic feature has been described with the ability to release VEGF, IL-8, and SDF-1. Methods: Recently, we have found that tumor infiltrating NKs in Non Small Cell Lung Cancer are enriched in the CD56brightCD16- NK cell subset characterized by a pro-angiogenic phenotype and functionality. We than moved to the phenotypic and functional characterization of fresh or 3 day-cultured NKs derived from pleural effusions (PE) of patients with primary or metastatic tumors of different origin, including mesothelioma and lung carcinoma. Results: We found that the CD56brightCD16- NK cell subset predominates in PE. Further, these NKs are able to generate a complex pro-angiogenic cytokine response, namely VEGF, IL-8, SDF-1, Osteopontin (OPN), and moderate/low levels of IFNg. However, they possess consistent amount of Perforin and are able to respond to IL-2 stimulation. Discussion: Here we present new data concerning a potential role of NKs in PE of patients with different types of tumors, in the tumor angiogenesis process. In fact these NKs are endowed both ex-vivo and after 3 day of IL-2 culture of high release potential of pro-angiogenic cytokines, such as VEGF, IL-8, SDF-1, and OPN. Conclusions: Although IL-2 therapy in cancer patients has been shown to have properties to rescue some activity of T and NK cells in vivo, with some encouraging clinical results, concerning cancer patients with PE onset, it would be taken into deep consideration the potential role of the pro-angiogenic and pro-tumor ability of NKs in PE. Bibliography: D.M. Noonan et al. Cancer Metastasis Rev. 2008; 27:31-40. A. Bruno et al. Neoplasia 2013, 15:133-142.
Natural killer cells from pleural effusions are responsive to interleukin-2 but are endowed with a potent pro-angiogenic feature
MORTARA, LORENZO;ZANELLATO, SILVIA;A. Bruno;IMPERATORI, ANDREA SELENITO;ROTOLO, NICOLA;DOMINIONI, LORENZO;NOONAN, DOUGLAS
2014-01-01
Abstract
Purpose: Natural Killer (NKs) cells are crucial effector cells of innate immunity able to kill tumor or virus-infected cells. However, in tumor-bearing host the anti-tumor function of NKs are largely impaired. Interestingly, in the early phase of pregnancy, a leading role of a NK cell subset (decidual NKs) with a potent pro-angiogenic feature has been described with the ability to release VEGF, IL-8, and SDF-1. Methods: Recently, we have found that tumor infiltrating NKs in Non Small Cell Lung Cancer are enriched in the CD56brightCD16- NK cell subset characterized by a pro-angiogenic phenotype and functionality. We than moved to the phenotypic and functional characterization of fresh or 3 day-cultured NKs derived from pleural effusions (PE) of patients with primary or metastatic tumors of different origin, including mesothelioma and lung carcinoma. Results: We found that the CD56brightCD16- NK cell subset predominates in PE. Further, these NKs are able to generate a complex pro-angiogenic cytokine response, namely VEGF, IL-8, SDF-1, Osteopontin (OPN), and moderate/low levels of IFNg. However, they possess consistent amount of Perforin and are able to respond to IL-2 stimulation. Discussion: Here we present new data concerning a potential role of NKs in PE of patients with different types of tumors, in the tumor angiogenesis process. In fact these NKs are endowed both ex-vivo and after 3 day of IL-2 culture of high release potential of pro-angiogenic cytokines, such as VEGF, IL-8, SDF-1, and OPN. Conclusions: Although IL-2 therapy in cancer patients has been shown to have properties to rescue some activity of T and NK cells in vivo, with some encouraging clinical results, concerning cancer patients with PE onset, it would be taken into deep consideration the potential role of the pro-angiogenic and pro-tumor ability of NKs in PE. Bibliography: D.M. Noonan et al. Cancer Metastasis Rev. 2008; 27:31-40. A. Bruno et al. Neoplasia 2013, 15:133-142.
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