TY - JOUR
T1 - Natural killer cells kill human melanoma cells with characteristics of cancer stem cells
AU - Pietra, Gabriella
AU - Manzini, Claudia
AU - Vitale, Massimo
AU - Balsamo, Mirna
AU - Ognio, Emanuela
AU - Boitano, Monica
AU - Queirolo, Paola
AU - Moretta, Lorenzo
AU - Mingari, Maria Cristina
PY - 2009
Y1 - 2009
N2 - Experimental and clinical data suggest that tumours harbour a cell population retaining stem cell characteristics that can drive tumorigenesis. CD133 is considered an important cancer stem cells (CSC)-associated marker. In a large variety of human malignancies, including melanoma, CD133+ cells have been reported to comprise CSC. In this study, we show that melanoma cell lines are highly heterogeneous for the expression of several stem cell-associated markers including CD133, c-kit/CD117 and p75 neurotrophin receptor/CD271. Since no information is available on the ability of NK cells to recognize and lyse melanoma stem cells, we assessed whether melanoma cell lines, characterized by stem cell-like features, were susceptible to lysis by IL-2-activated NK cells. We show that activated NK cells efficiently kill malignant melanoma cell lines that were enriched in putative CSC by the use of different selection methods (i.e. CD133 expression, radioresistance or the ability to form melanospheres in stem cell-supportive medium). NK cell-mediated recognition and lysis of melanoma cells involved different combinations of activating NK receptors. Since CSC have been reported to be both drug resistant and radioresistant, our present data suggest that NK-based adoptive immunotherapy could represent a novel therapeutic approach to possibly eradicate metastatic melanoma.
AB - Experimental and clinical data suggest that tumours harbour a cell population retaining stem cell characteristics that can drive tumorigenesis. CD133 is considered an important cancer stem cells (CSC)-associated marker. In a large variety of human malignancies, including melanoma, CD133+ cells have been reported to comprise CSC. In this study, we show that melanoma cell lines are highly heterogeneous for the expression of several stem cell-associated markers including CD133, c-kit/CD117 and p75 neurotrophin receptor/CD271. Since no information is available on the ability of NK cells to recognize and lyse melanoma stem cells, we assessed whether melanoma cell lines, characterized by stem cell-like features, were susceptible to lysis by IL-2-activated NK cells. We show that activated NK cells efficiently kill malignant melanoma cell lines that were enriched in putative CSC by the use of different selection methods (i.e. CD133 expression, radioresistance or the ability to form melanospheres in stem cell-supportive medium). NK cell-mediated recognition and lysis of melanoma cells involved different combinations of activating NK receptors. Since CSC have been reported to be both drug resistant and radioresistant, our present data suggest that NK-based adoptive immunotherapy could represent a novel therapeutic approach to possibly eradicate metastatic melanoma.
KW - Cancer stem cells
KW - CD133
KW - Melanoma
KW - Melanospheres
KW - NK cells
UR - http://www.scopus.com/inward/record.url?scp=67649864077&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67649864077&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxp047
DO - 10.1093/intimm/dxp047
M3 - Article
C2 - 19491215
AN - SCOPUS:67649864077
VL - 21
SP - 793
EP - 801
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 7
ER -