Killer cell Ig-like receptors ligand-mismatched, alloreactive natural killer cells lyse primary solid tumors.
BACKGROUND
Donor alloreactive natural killer (NK) cells have a potent antileukemic effect in haploidentical stem cell transplantation. Whether alloreactive NK cells are able to specifically kill fresh tumor cells from primary solid tumors was analyzed.


METHODS
NK cells were purified from healthy donors for the expression of inhibitory killer cell immunoglobulin (Ig)-like receptors (KIRs), ex vivo expanded, and used as effector cells. Their cytotoxic effect on tumor cells freshly obtained from surgical specimens was assessed by means of a single-cell cytotoxic assay (SCCA).


RESULTS
Tumor cells from 1 ovarian, 1 gastric, 3 colon, and 4 renal cell cancers were analyzed and found susceptible to alloreactive NK cell killing (>20% lysis at an effector cell to target cell [E:T] ratio of 10:1 for tumor cells not expressing at least 1 human lymphocyte antigen [HLA] class I KIR-ligand group). Remarkably, NK cells that recognized specific HLA-C group mismatches were able to kill HLA-C KIR ligand-mismatched tumor cells, whereas no lysis of target cells occurred with KIR ligand-matched tumor targets.


CONCLUSIONS
Alloreactive NK-cell mediated antitumor effects might provide useful insights for designing new cell therapy approaches against solid tumors.
Re
Francesca
F
Department of Oncology, Scientific Institute San Raffaele, Milan, Italy.
Staudacher
Carlo
C
Zamai
Loris
L
Vecchio
Viviana
V
Bregni
Marco
M
D000970:Antineoplastic Agents / Q000276:immunology*; D017209:Apoptosis; D001681:Biological Assay / Q000379:methods*; D045744:Cell Line, Tumor; D017690:Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D008024:Ligands; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D014184:Transplantation, Homologous
D000970:Antineoplastic Agents; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR