Arienti F, Gambacorti-Passerini C, Borin L, Rivoltini L, Orazi A, Pogliani E M, Corneo G, Parmiani G
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Ann Oncol. 1992 Feb;3(2):155-62. doi: 10.1093/oxfordjournals.annonc.a058133.
The NK and LAK activity of peripheral blood lymphocytes of leukemic patients as well as the susceptibility of their acute myeloid (AML) and lymphoblastic (ALL) leukemia cells to autologous and allogeneic LAKs were examined. In addition, neoplastic cells at diagnosis and at relapse were compared in the same patients for several features, including in vitro susceptibility to LAKs and to the drugs used in the induction phase, expression of MDR phenotype and of adhesion molecules, and differentiation markers. The NK activity of patients' LAK cells on K562 was significantly lower than that of a group of healthy donors whereas no differences were found in LAK activity as evaluated on Daudi cells. Three of 5 AML and 3 of 4 ALL were significantly more susceptible to autologous and allogeneic LAK lysis when blasts obtained at relapse were compared with leukemic cells of the same patients at diagnosis. This different lysability was not associated with in vitro modified sensitivity to drugs used in induction treatment. Moreover, no elevation in the expression of the multidrug-resistance (MDR)-related P170 glycoprotein was noted in relapsing leukemic cells. Even the expression of adhesion molecules and differentiation markers did not correlate with lysability of leukemic cells. These data demonstrate that relapsing leukemic blasts can be significantly lysed by LAK cells and suggest a rationale for adoptive immunotherapy with IL-2 and LAK cells in the treatment of acute leukemic patients.
检测了白血病患者外周血淋巴细胞的NK和LAK活性,以及其急性髓细胞白血病(AML)和淋巴细胞白血病(ALL)细胞对自体和异体LAK细胞的敏感性。此外,还比较了同一患者诊断时和复发时肿瘤细胞的几个特征,包括体外对LAK细胞和诱导期所用药物的敏感性、多药耐药(MDR)表型和黏附分子的表达以及分化标志物。患者LAK细胞对K562的NK活性显著低于一组健康供体,而在Daudi细胞上评估的LAK活性未发现差异。与诊断时同一患者的白血病细胞相比,5例AML中的3例和4例ALL中的3例在复发时获得的原始细胞对自体和异体LAK裂解更敏感。这种不同的可裂解性与诱导治疗中所用药物的体外敏感性改变无关。此外,复发白血病细胞中未发现多药耐药(MDR)相关P170糖蛋白表达升高。甚至黏附分子和分化标志物的表达也与白血病细胞的可裂解性无关。这些数据表明复发白血病原始细胞可被LAK细胞显著裂解,并为在急性白血病患者治疗中采用IL-2和LAK细胞进行过继性免疫治疗提供了理论依据。