Purpose: Immune cells infiltrating tumors often show a polarized phenotype that reflects attenuation of anti-tumor activity and enhancement of pro-tumor activities, including angiogenesis. Natural Killer (NKs) cells are effector lymphocytes of innate immunity that can potentially control tumors by their cytotoxic activity and their ability to produce IFNg. However, a NK cell subset that accumulates in the decidua has a peculiar CD56superbrightCD16- phenotype that produce large amounts of pro-angiogenic factors. Methods: We recently reported that tumor infiltrating NK cells (TINKs) in Non Small Cell Lung Cancer, are enriched in the CD56brightCD16- NK cell subset, produce VEGF, PlGF and IL-8, and activate endothelial cells towards a pro-angiogenic phenotype. This angiogenic switch seems to be in part due to TGFb within the tumor microenvironment. Here, we investigate the NK phenotypes and functional distributions in tumor samples, adjacent normal tissues and peripheral bloods from Colo-Rectal Cancer (CRC) patients. Results: We found that the CD56brightCD16- NK cell subset predominates over the cytotoxic CD56dimCD16+ subset and produces high level of VEGF, moderate IL-8 and low amounts of IFNg. Further, our preliminary results, investigating the expression of decidual NK-like surface markers like CD9 and CD49a, indicated that only NKs, in tumor and peri-tumoral, have increased expression of both markers. Moreover, although the NKp44 marker seem to be up-regulated, the NKG2D activatory receptor results strongly down-regulated in TINKs. Discussion: Together these findings strongly suggest a pro-angiogenic role of CRC-derived NKs, while their anti-tumor response in the tumor milieu, as IFN response and cytotoxicity, is largely inhibited. Conclusions: Here we present data on phenotypic and functional features of TINKs in CRC patients and put new hints on how they potentially are involved in the tumor angiogenesis. Bibliography: A. Bruno et al. Neoplasia 2013, 15:133-142.

Natural killer cells infiltrating colo-rectal cancer are switched towards the decidual-like pro-angiogenic CD56brightCD16- NK cell subset

A. Bruno;PAGANI, ARIANNA;ZANELLATO, SILVIA;DOMINIONI, LORENZO;NOONAN, DOUGLAS;MORTARA, LORENZO
2014

Abstract

Purpose: Immune cells infiltrating tumors often show a polarized phenotype that reflects attenuation of anti-tumor activity and enhancement of pro-tumor activities, including angiogenesis. Natural Killer (NKs) cells are effector lymphocytes of innate immunity that can potentially control tumors by their cytotoxic activity and their ability to produce IFNg. However, a NK cell subset that accumulates in the decidua has a peculiar CD56superbrightCD16- phenotype that produce large amounts of pro-angiogenic factors. Methods: We recently reported that tumor infiltrating NK cells (TINKs) in Non Small Cell Lung Cancer, are enriched in the CD56brightCD16- NK cell subset, produce VEGF, PlGF and IL-8, and activate endothelial cells towards a pro-angiogenic phenotype. This angiogenic switch seems to be in part due to TGFb within the tumor microenvironment. Here, we investigate the NK phenotypes and functional distributions in tumor samples, adjacent normal tissues and peripheral bloods from Colo-Rectal Cancer (CRC) patients. Results: We found that the CD56brightCD16- NK cell subset predominates over the cytotoxic CD56dimCD16+ subset and produces high level of VEGF, moderate IL-8 and low amounts of IFNg. Further, our preliminary results, investigating the expression of decidual NK-like surface markers like CD9 and CD49a, indicated that only NKs, in tumor and peri-tumoral, have increased expression of both markers. Moreover, although the NKp44 marker seem to be up-regulated, the NKG2D activatory receptor results strongly down-regulated in TINKs. Discussion: Together these findings strongly suggest a pro-angiogenic role of CRC-derived NKs, while their anti-tumor response in the tumor milieu, as IFN response and cytotoxicity, is largely inhibited. Conclusions: Here we present data on phenotypic and functional features of TINKs in CRC patients and put new hints on how they potentially are involved in the tumor angiogenesis. Bibliography: A. Bruno et al. Neoplasia 2013, 15:133-142.
Bruno, A.; Pagani, Arianna; Zanellato, Silvia; Canali, S.; Dominioni, Lorenzo; Cassinotti, E.; David, G.; Albini, A.; Noonan, Douglas; Mortara, Lorenzo
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/1929120
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