PURPOSE: Natural killer (NK) cells are lymphocytes involved in tumor recognition and eradication. NK activity is impaired in cancer patients and in NSCLC showed a pro-angiogenic phenotype and function. We investigated whether NK cells infiltrating inflammatory or malignant pleural effusions (iPE or mPE) are able to acquire pro-angiogenic features. METHODS: We performed ex vivo FACS analysis of phenotype and cytokine production of PE-derived NK cells (PE-NKs) and a CD107a assay to evaluate their cytotoxicity. RESULTS: PE-NKs are enriched in CD56brightCD16- NK cells. These NK cells express the decidual NK marker CD49a and the activation marker CD69. Moreover, PE-NKs showed very low expression of the CD57 maturation marker. NK cells from all patient samples showed lower cytotoxicity against K562 target cells in comparison to peripheral blood of healthy donors (hPB) NKs. After 3-day NK culture with IL-2, PE-NKs restored their cytotoxicity, whereas in NK from peripheral blood of patients did not reach a high level of killing capacity. 3-day culture using IL-2 plus TGFb or IL-2 in a iPE/mPE conditioned medium (CM) only partially restored cytotoxic potential. Purified hPB NK cells treated for 7 days with IL-15 in a iPE/mPE-CM acquired a pro-angiogenic phenotype, showing polarization towards the CD56brightCD16dimIFNglow NK subset. DISCUSSION AND CONCLUSIONS: NK cells from mPE display pro-angiogenic features and mPE-CM was able to polarize healthy PB NK cells in vitro towards the pro-angiogenic CD56brightCD16- NK subset, suggesting that in the PE milieu, diverse soluble factors are able to skew cytotoxic NK cells into pro-tumor, pro-angiogenic NK cells. BIBLIOGRAPHY: Bruno et al. The proangiogenic phenotype of natural killer cells in patients with non-small cell lung cancer. Neoplasia. 2013 Feb;15(2):133-42. Mortara et al. Polarization of tumor infiltrating leukocytes from innate immunity and their role in the pro-angiogenic phenotype in NSCLC. J. Clin. Cell. Immunol., 6:2, 2015.
Natural killer cells from patients with either malignant or inflammatory pleural effusions display decreased cytotoxic capacity and decidual-like phenotype
ZANELLATO, SILVIA;Bruno, A.;BASSANI, BARBARA;CATTONI, MARIA ANGELA;IMPERATORI, ANDREA SELENITO;NOONAN, DOUGLAS;MORTARA, LORENZO
2016-01-01
Abstract
PURPOSE: Natural killer (NK) cells are lymphocytes involved in tumor recognition and eradication. NK activity is impaired in cancer patients and in NSCLC showed a pro-angiogenic phenotype and function. We investigated whether NK cells infiltrating inflammatory or malignant pleural effusions (iPE or mPE) are able to acquire pro-angiogenic features. METHODS: We performed ex vivo FACS analysis of phenotype and cytokine production of PE-derived NK cells (PE-NKs) and a CD107a assay to evaluate their cytotoxicity. RESULTS: PE-NKs are enriched in CD56brightCD16- NK cells. These NK cells express the decidual NK marker CD49a and the activation marker CD69. Moreover, PE-NKs showed very low expression of the CD57 maturation marker. NK cells from all patient samples showed lower cytotoxicity against K562 target cells in comparison to peripheral blood of healthy donors (hPB) NKs. After 3-day NK culture with IL-2, PE-NKs restored their cytotoxicity, whereas in NK from peripheral blood of patients did not reach a high level of killing capacity. 3-day culture using IL-2 plus TGFb or IL-2 in a iPE/mPE conditioned medium (CM) only partially restored cytotoxic potential. Purified hPB NK cells treated for 7 days with IL-15 in a iPE/mPE-CM acquired a pro-angiogenic phenotype, showing polarization towards the CD56brightCD16dimIFNglow NK subset. DISCUSSION AND CONCLUSIONS: NK cells from mPE display pro-angiogenic features and mPE-CM was able to polarize healthy PB NK cells in vitro towards the pro-angiogenic CD56brightCD16- NK subset, suggesting that in the PE milieu, diverse soluble factors are able to skew cytotoxic NK cells into pro-tumor, pro-angiogenic NK cells. BIBLIOGRAPHY: Bruno et al. The proangiogenic phenotype of natural killer cells in patients with non-small cell lung cancer. Neoplasia. 2013 Feb;15(2):133-42. Mortara et al. Polarization of tumor infiltrating leukocytes from innate immunity and their role in the pro-angiogenic phenotype in NSCLC. J. Clin. Cell. Immunol., 6:2, 2015.
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