Martner Anna, Rydström Anna, Riise Rebecca E, Aurelius Johan, Brune Mats, Foà Robin, Hellstrand Kristoffer, Thorén Fredrik B
TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg 405 30, Sweden.
Department of Hematology, University of Gothenburg, Gothenburg 413 45, Sweden.
Oncotarget. 2015 Dec 15;6(40):42569-74. doi: 10.18632/oncotarget.5559.
In a phase IV trial, eighty-four patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose human recombinant interleukin-2 (IL-2) to prevent relapse in the post-consolidation phase. Aspects of natural killer (NK) cell biology were analyzed before and during immunotherapy with focus on outcome in older patients. In younger (<60 years old, n = 37) and older patients (>60 years old, n = 47), treatment with HDC/IL-2 resulted in an expansion of CD56(bright) and CD16+ NK cells in blood along with an increased NK cell expression of the natural cytotoxicity receptors (NCR) NKp30 and NKp46. In older patients, a high expression of NKp30 or NKp46 on CD16+ NK cells before and during therapy predicted leukemia-free and overall survival. These results suggest that NK cell functions determine relapse risk and survival in older AML patients and point to biomarkers of efficacy in protocols for remission maintenance.
在一项IV期试验中,84例年龄在18 - 79岁、处于首次完全缓解(CR)期的急性髓系白血病(AML)患者接受了组胺二盐酸盐(HDC)和低剂量人重组白细胞介素-2(IL-2)的免疫治疗周期,以预防巩固治疗后的复发。在免疫治疗前和治疗期间分析了自然杀伤(NK)细胞生物学的各个方面,重点关注老年患者的治疗结果。在年轻患者(<60岁,n = 37)和老年患者(>60岁,n = 47)中,HDC/IL-2治疗导致血液中CD56(bright)和CD16 + NK细胞扩增,同时自然细胞毒性受体(NCR)NKp30和NKp46的NK细胞表达增加。在老年患者中,治疗前和治疗期间CD16 + NK细胞上NKp30或NKp46的高表达预示着无白血病生存期和总生存期。这些结果表明,NK细胞功能决定老年AML患者的复发风险和生存期,并指出了缓解期维持方案中疗效的生物标志物。