Cancer Biotherapy Center, Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, China.
Cancer Biother Radiopharm. 2010 Dec;25(6):741-6. doi: 10.1089/cbr.2010.0770.
Killer immunoglobulin-like receptor (KIR)-ligand incompatibility in the graft-versus-host direction is associated with improved outcome in patients receiving hematopoietic stem cell transplants. Fetal-maternal microchimerism has been suggested to mediate acquired fetal-maternal tolerance. The goal of this study was to determine the clinical efficacy of KIR-ligand incompatibility and fetal-maternal microchimerism for interleukin-2-activated haploidentical peripheral blood stem cells (haplo-PBSCs) treatment for patients with advanced solid cancer. Forty-two (42) patients with advanced stage of solid cancer and refractory to standard chemotherapy were treated with haplo-PBSCs donated by their parents or children. Human leukocyte antigen typing, fetal-maternal microchimerism status, and engraftment were detected. Clinical outcomes including overall survival (OS), progression-free survival (PFS), and Karnofsky Performance Status (KPS) level were evaluated. Patients receiving haplo-PBSCs treatment with KIR-ligand incompatibility in the graft-versus-host direction had higher probability of OS (26.8 ± 3.1 months) and PFS (13.4 ± 1.3 months) when compared with those with KIR ligand compatibility (OS: 17.4 ± 3.0 months, p < 0.05 and PSF: 8.0 ± 0.9 months, p < 0.05). Further, OS (31.2 ± 4.3 months), PFS (14.7 ± 2.2 months), and KPS increase (27 points) in the microchimerism-positive group was improved compared with that in the microchimerism-negative group (OS: 16.9 ± 3.8 months, p < 0.01, PFS: 5.6 ± 1.4 months, p < 0.01, and KPS increase: 15 points, p < 0.01). Therefore, KIR-ligand incompatibility and fetal-maternal microchimerism are associated with better outcome for haplo-PBSCs treatment.
杀伤细胞免疫球蛋白样受体 (KIR)-配体不相容性在移植物抗宿主方向与接受造血干细胞移植的患者的改善结局相关。已经提出胎儿-母体微嵌合体来介导获得性胎儿-母体耐受。本研究的目的是确定 KIR 配体不相容性和胎儿-母体微嵌合体对白细胞介素-2 激活的单倍体外周血干细胞（haplo-PBSCs）治疗晚期实体癌患者的临床疗效。42 名（42 名）患有晚期实体癌且对标准化疗耐药的患者接受其父母或子女捐献的 haplo-PBSCs 治疗。检测人白细胞抗原分型、胎儿-母体微嵌合体状态和植入情况。评估包括总生存（OS）、无进展生存（PFS）和卡氏功能状态（KPS）水平在内的临床结局。与 KIR 配体相容的患者相比，在移植物抗宿主方向具有 KIR 配体不相容性的接受 haplo-PBSCs 治疗的患者具有更高的 OS（26.8±3.1 个月）和 PFS（13.4±1.3 个月）的可能性（OS：17.4±3.0 个月，p<0.05；PSF：8.0±0.9 个月，p<0.05）。此外，微嵌合体阳性组的 OS（31.2±4.3 个月）、PFS（14.7±2.2 个月）和 KPS 增加（27 分）均优于微嵌合体阴性组（OS：16.9±3.8 个月，p<0.01；PFS：5.6±1.4 个月，p<0.01；KPS 增加：15 分，p<0.01）。因此，KIR 配体不相容性和胎儿-母体微嵌合体与 haplo-PBSCs 治疗的更好结局相关。
