title: Natural killer cells can exert a graft-vs-tumor effect in haploidentical stem cell transplantation for pediatric solid tumors.
abstract: Little progress has been made with regard to the survival of children with metastatic and refractory solid tumors. Preliminary data from haploidentical stem cell transplantation (haplo-SCT) suggested a clinically beneficial allograft-vs-tumor effect associated with natural killer cell (NK) donor-recipient mismatch. We hypothesized that interaction between activatory receptors on NK cells and their ligands on tumor cells could be also important. To evaluate the NK-cell-mediated allograft-vs-tumor effect, we conducted a pilot study of haplo-SCT on six children with refractory solid tumors. Our specific goal for this study was NKG2D-major histocompatibility complex class I-related chain A interaction. Tasks include specific immunoassays that support haplo-SCT in refractory solid tumors. Patients suffered from neuroblastoma (n = 1), Ewing sarcoma (n = 2), a desmoplastic tumor (n = 1), nasopharyngeal carcinoma (n = 1), and embryonal rhabdomyosarcoma (n = 1). Pretransplantation disease status showed progressive disease in 2 patients, partial remission in 2 patients, and complete remission in 2 patients. NK-cell mismatch was present in three donor-recipients. Ligands for NKG2D receptors, major histocompatibility complex class I-related chain A and UL16 binding protein 2 were overexpressed in six of six and four of six tumors, respectively. NK cells led early immune reconstitution. After haplo-SCT, three patients were in complete remission, one patient showed partial remission, and two patients were in stable disease. With a median follow-up of 14 months, three patients were alive and in complete remission, and three patients had died; two due to progressive disease and one of transplant-related toxicity. Blocking NKG2D-major histocompatibility complex class I-related chain A interaction in vitro reduced NK-cell cytotoxicity. Our preliminary results suggest a beneficial effect from haplo-SCT in refractory solid tumors.
authors: Department of Hemato-Oncology and Stem Cell Transplantation, Hospital Infantil Universitario Niño Jesús, Madrid, Spain. aperezm.hnjs@salud.madrid.org
authors: Antonio
authors: A
authors: Pérez-Martínez
authors: Inmaculada
authors: I
authors: de Prada Vicente
authors: Lucía
authors: L
authors: Fernández
authors: Marta
authors: M
authors: González-Vicent
authors: Jaime
authors: J
authors: Valentín
authors: Roberto
authors: R
authors: Martín
authors: Hannah
authors: H
authors: Maxwell
authors: Julián
authors: J
authors: Sevilla
authors: José Luis
authors: JL
authors: Vicario
authors: Miguel Ángel
authors: MÁ
authors: Díaz
mesh_terms: D002648:Child; D005434:Flow Cytometry; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D016133:Polymerase Chain Reaction / Q000379:methods