natural killer lysis receptor (nklr)nklr-ligand matching as a novel approach for enhancing anti-tumor activity of allogeneic nk cells自然杀伤细胞溶解受体(nklr)nklr-ligand匹配作为增强抗肿瘤的新方法同种异体nk细胞的活性.pdfVIP

Natural Killer Lysis Receptor (NKLR)/NKLR-Ligand Matching as a Novel Approach for Enhancing Anti-Tumor Activity of Allogeneic NK Cells 1,2,3 1 1 1 1 1 Gal Markel *, Rachel Seidman , Michal J. Besser , Naama Zabari , Rona Ortenberg , Ronnie Shapira , 1 4 5 6 1 Avraham J. Treves , Ron Loewenthal , Arie Orenstein , Arnon Nagler , Jacob Schachter 1 Ella Institute of Melanoma, Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel, 2 Talpiot Medical Leadership Program, Sheba Medical Center, Ramat Gan, Israel, 3 Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, 4 Tissue Typing Laboratory, Sheba Medical Center, Ramat Gan, Israel, 5 Center for Advanced Technologies, Sheba Medical Center, Ramat Gan, Israel, 6 Institute of Hematology, Sheba Medical Center, Ramat Gan, Israel Abstract Background: NK cells are key players in anti tumor immune response, which can be employed in cell-based therapeutic modalities. One of the suggested ways to amplify their anti tumor effect, especially in the field of stem cell transplantation, is by selecting donor/recipient mismatches in specific HLA, to reduce the inhibitory effect of killer Ig-like receptors (KIRs). Here we suggest an alternative approach for augmentation of anti tumor effect of allogeneic NK cells, which is founded on profile matching of donor NK lysis receptors (NKLR) phenotype with tumor lysis-ligands. Methodology/Principal Findings: We show that an NKLR-mediated killing directly correlates with the NKLR expression intensity on NK cells. Considerable donor variability in the expres