Natural killer cells can exert a graft-vs-tumor effect in haploidentical stem cell transplantation for pediatric solid tumors

• Published in: Experimental hematology 2012-11, Vol.40 (11), p.882-891.e1
• Main Authors: Pérez-Martínez, Antonio, de Prada Vicente, Inmaculada, Fernández, Lucía, González-Vicent, Marta, Valentín, Jaime, Martín, Roberto, Maxwell, Hannah, Sevilla, Julián, Vicario, José Luis, Díaz, Miguel Ángel
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Child; Flow Cytometry; Haplotypes; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Killer Cells, Natural - immunology; Neoplasms - immunology; Neoplasms - pathology; Neoplasms - surgery; Polymerase Chain Reaction - methods
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2012.07.004

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.