Foa R, Fierro M T, Cesano A, Guarini A, Bonferroni M, Raspadori D, Miniero R, Lauria F, Gavosto F
Dipartimento di Scienze Biomediche e Oncologia Umana, University of Torino, Italy.
Blood. 1991 Aug 15;78(4):1041-6.
In 26 myeloid and lymphoid acute leukemia patients at presentation the capacity to generate interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) cells effective against the natural killer (NK)-resistant Raji cell line, as well as the susceptibility of the blasts to normal peripheral blood (PB) LAK cells and to autologous LAK effectors was analyzed. The overall PB LAK activity against Raji cells was significantly lower in acute leukemia patients compared with normal controls (mean, 1,473 +/- 971 SD LU/10(8) LAK effectors v 3,340 +/- 1,862; P less than .001). The sensitivity of the blasts to autologous LAK cells was also significantly lower than to normal LAK effectors (517 +/- 593 LU/10(8) LAK effectors v 1,304 +/- 1,066; P less than .01). When the data were analyzed independently, four patterns of behavior could be recognized. The relatively largest group (9 of 26) included patients in whom effective LAK cells could be generated against the Raji line, but in whom the blasts were resistant to autologous PB-LAK effectors while being susceptible to normal LAK cells (defective specific LAK activity). In 5 of 26 cases, an incapacity to generate LAK activity against both allogeneic and autologous target cells was observed (defective LAK generation). In six further cases, the blasts were resistant to both allogeneic and autologous LAK populations, though the latter were effective against the Raji line (resistant blasts). The same defects could also be shown with bone marrow-derived LAK cells. Only in six cases did the leukemic blasts appear susceptible to autologous and allogeneic LAK cells. In four patients the analysis could be repeated at remission, and in three a restoration of the LAK function against the primary blasts was recorded. In the 10 cases studied at relapse, the blasts were resistant to autologous LAK effectors in nine and to normal LAK in seven. These data demonstrate that in most acute leukemia patients with active disease, a defect of the LAK machinery, either a deficient generation of LAK cells or the resistance of the blasts to LAK effectors, may be documented, pointing therefore to a possible contributory role of the LAK system in the control of leukemic cell growth. In view of the frequent normalization of the autologous LAK activity at the time of remission, immunotherapy with IL-2/LAK cells should be primarily aimed to patients with minimal residual disease.
对26例初诊的髓系和淋巴系急性白血病患者生成白细胞介素-2（IL-2）诱导的、对自然杀伤（NK）抵抗的拉吉细胞系有效的淋巴因子激活的杀伤（LAK）细胞的能力，以及原始细胞对正常外周血（PB）LAK细胞和自体LAK效应细胞的敏感性进行了分析。与正常对照相比，急性白血病患者针对拉吉细胞的总体PB LAK活性显著降低（平均值，1473±971 SD LU/10⁸ LAK效应细胞对3340±1862；P＜0.001）。原始细胞对自体LAK细胞的敏感性也显著低于对正常LAK效应细胞的敏感性（517±593 LU/10⁸ LAK效应细胞对1304±1066；P＜0.01）。当对数据进行单独分析时，可以识别出四种行为模式。相对最大的一组（26例中的9例）包括那些能够生成针对拉吉细胞系的有效LAK细胞，但原始细胞对自体PB-LAK效应细胞耐药而对正常LAK细胞敏感的患者（特异性LAK活性缺陷）。在26例中的5例中，观察到无法生成针对同种异体和自体靶细胞的LAK活性（LAK生成缺陷）。在另外6例中，原始细胞对同种异体和自体LAK群体均耐药，尽管后者对拉吉细胞系有效（耐药原始细胞）。骨髓来源的LAK细胞也可显示出相同的缺陷。只有6例白血病原始细胞似乎对自体和同种异体LAK细胞敏感。在4例患者中，缓解期可重复进行分析，其中3例记录到针对原始细胞的LAK功能恢复。在复发时研究的1例患者中，9例原始细胞对自体LAK效应细胞耐药，7例对正常LAK耐药。这些数据表明，在大多数患有活动性疾病的急性白血病患者中，可以证明存在LAK机制缺陷，要么是LAK细胞生成不足，要么是原始细胞对LAK效应细胞耐药，因此表明LAK系统在控制白血病细胞生长中可能起作用。鉴于缓解期自体LAK活性经常恢复正常，IL-2/LAK细胞免疫疗法应主要针对微小残留病患者。
