Both CD133+ and CD133- medulloblastoma cell lines express ligands for triggering NK receptors and are susceptible to NK-mediated cytotoxicity.
Adoptive cellular immunotherapy has been proposed as an additional treatment of medulloblastoma, an intracranial tumor characterized by a particularly poor prognosis. However, little is known on the ability of the immune system to effectively attack this tumor. In this study, we show that activated human NK cells efficiently kill medulloblastoma cell lines in vitro. NK-mediated killing involved different activating receptors (including NKp46, NKp30, DNAM-1 and NKG2D) and correlated with the presence of their specific ligands on tumor cells. In contrast, the absence of major adhesion interactions, such as LFA-1/ICAM did not impair the NK-mediated cytotoxicity. Medulloblastoma expressed a number of tumor-associated molecules including CD146 and CD133, considered a marker for cancer stem cells. Remarkably, both CD133-positive and CD133-negative cell lines were susceptible to lysis. Tumor cells also expressed molecules that are currently used as diagnostic tools for neuroblastoma cell identification. In particular, B7 homolog 3 (B7-H3) was expressed by all the medulloblastoma cell lines analyzed, while the presence of GD(2) and NB84 was restricted to given cell lines and/or marked a defined tumor cell subset.
Castriconi
Roberta
R
Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genova, Italy.
Dondero
Alessandra
A
Negri
Francesca
F
Bellora
Francesca
F
Nozza
Paolo
P
Carnemolla
Barbara
B
Raso
Alessandro
A
Moretta
Lorenzo
L
Moretta
Alessandro
A
Bottino
Cristina
C
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008527:Medulloblastoma / Q000276:immunology* / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D008024:Ligands; C000606023:PROM1 protein, human; D010455:Peptides; D011971:Receptors, Immunologic