Effect of KIR/HLA receptor-ligand mode on prognosis of single unrelated cord blood transplantation in patients with hematological malignancies / 中华血液学杂志

Objective: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT) . Methods: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2) . Group 2 (n=96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2) . Results: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1-62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG) . The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%, the median time of neutrophil engraftment for group 1 and 2 was 16 (10-41) days vs 17 (11-33) days (P=0.705) . The ratio of platelet engraftment was 88.5% for group 1 and 87.5% for group 2, the median time of platelet engraftment was 35 (11-113) days vs 38.5 (13-96) days (P=0.317) . The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7% (95%CI 31.4%-45.9%) for group 1 and 50.0% (95%CI 39.6%-59.6%) for group 2 (P=0.075) , but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P=0.036) . Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2) : 17.7% (95%CI 11.7%-24.9%) vs 22.7% (95%CI 4.4%-32.2%) after 3 years (P=0.288) . The median follow-up time was 742 (335-2 512) days. The 3-year OS was 72.1% for group 1 and 60.5% for group 2 (P=0.079) . There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9% (95%CI 56.2%-72.3%) vs 55.4% (95%CI 44.4%-65.0%) (χ(2)=3.027, P=0.082) ]. Non-relapse mortality for group 1 was 12.1% (95%CI 7.7%-17.4%) and for group 2 was 16.7% (95%CI 10.0%-24.8%) (P=0.328) . Conclusion: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.

Expression and abscission of activated receptors and their ligands on/from NK cells in peripheral blood of patients with acute leukemia / 中国实验血液学杂志

This study was aimed to explore the immune escaping mechanisms based on expression and abscission of human natural killer (NK) cell activating receptors NKG2D and their ligands MICA/B, ULBP-1, 2, 3 in patients with acute leukemia (AL). 30 de novo AL patients and 10 healthy persons (control) were enrolled in study. Flow cytometry was used to detect the expression levels of MICA/B, ULBP-1, 2, 3 on leukemic cells. ELISA was used to detect the levels of soluble MICA (sMICA), solube MICB (sMICB) and soluble ULBP-1, -2, -3 in the serum. The results showed that sMICA, sMICB and ULBP-1, -2, -3 were not expressed or expressed at very low levels on leukemia cells of the patients; the levels of free sMICA and sMICB in serum of AL patients were higher than that in serum of healthy persons, there was significant difference (p<0.01). But the levels of ULBP 1-3 in serum of AL patients did not show obvious statistical difference as compared with healthy persons (p>0.05). It is concluded that the negative or low expression of NKG2D ligands (MICA, MICB and ULBPs) on surface of acute leukemia cells may lead to the immune escape of leukemia cells, the abscission of MICA and MICB, and the deficiency of ULBP expression on leukemia cells may be one of immune escape mechanisms of leukemia cells.