Sandoval-Borrego Daniela, Moreno-Lafont Martha C, Vazquez-Sanchez Ernesto Antonio, Gutierrez-Hoya Adriana, López-Santiago Rubén, Montiel-Cervantes Laura A, Ramírez-Saldaña Maricela, Vela-Ojeda Jorge
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México.
Cátedra CONACYT, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México, México.
Arch Med Res. 2016 Jan;47(1):55-64. doi: 10.1016/j.arcmed.2016.02.001. Epub 2016 Feb 12.
Natural killer (NK) cells are innate immune system cells that are actively involved in immune-surveillance of tumor cells. Recognition of tumors by NK cells occurred via natural cytotoxicity receptors and killer cell immunoglobulin-like receptors. Some ligands of the activating receptors seem to be present on malignant cells from patients with acute myeloid leukemia. The aim of the study was to evaluate the expression of activating receptors such as NKG2D, DNAM-1, NKp30, and NKp46, and inhibitory receptors such as NKG2A, CD158b, CD158a, and CD158e1 on NK cells from patients with newly diagnosed acute myeloid leukemia before and after stimulation with IL-2 and IL-12.
Patients were divided into two groups: group 1 AML M3, and group 2 non-M3 AML. Flow cytometry was performed on whole PBMC to evaluate NK cell receptors.
Twenty one AML patients, aged 26-78 years, and 11 matched healthy individuals were studied. NKG2D, and NKp46 expression was decreased in group 1 (p <0.019). Patients in Group 2 showed underexpression of the activating receptors NKp46. Differences after stimulation of NK cells with IL-2 and IL-12 were observed only in Group 2, in which a significant decrease in the expression of NKp46 receptor was found (p <0.0016). Patients in groups 1 and 2 showed overexpression of the inhibitory receptors CD158b (p <0.007) and NKG2A (p <0.01).
NKG2D receptor expression is decreased in patients with AML M3. In addition, patients with all FAB types of AML have overexpression of inhibitory receptors such as CD158b and NKG2A and decreased expression of the activating receptor NKp46.
自然杀伤(NK)细胞是先天性免疫系统细胞,积极参与对肿瘤细胞的免疫监视。NK细胞通过自然细胞毒性受体和杀伤细胞免疫球蛋白样受体识别肿瘤。一些激活受体的配体似乎存在于急性髓系白血病患者的恶性细胞上。本研究的目的是评估新诊断的急性髓系白血病患者在白细胞介素-2(IL-2)和白细胞介素-12(IL-12)刺激前后,NK细胞上激活受体如NKG2D、DNAX辅助分子-1(DNAM-1)、自然杀伤细胞p30(NKp30)和自然杀伤细胞p46(NKp46)以及抑制受体如NKG2A、CD158b、CD158a和CD158e1的表达情况。
患者分为两组:第1组为急性早幼粒细胞白血病(AML M3),第2组为非M3型AML。对全血单个核细胞(PBMC)进行流式细胞术检测以评估NK细胞受体。
研究了21例年龄在26 - 78岁的AML患者和11例匹配的健康个体。第1组中NKG2D和NKp46表达降低(p <0.019)。第2组患者的激活受体NKp46表达不足。仅在第2组中观察到用IL-2和IL-12刺激NK细胞后的差异,其中发现NKp46受体表达显著降低(p <0.0016)。第1组和第2组患者的抑制受体CD158b(p <0.007)和NKG2A(p <0.01)表达上调。
AML M3患者的NKG2D受体表达降低。此外,所有FAB分型的AML患者均有抑制受体如CD158b和NKG2A的表达上调以及激活受体NKp46的表达降低。