Foa R, Fierro M T, Raspadori D, Bonferroni M, Cardona S, Guarini A, Tos A G, di Celle P F, Cesano A, Matera L
Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Clinica Medica, University of Torino, Italy.
Blood. 1990 Oct 1;76(7):1349-54.
The capacity to generate lymphokine-activated killer (LAK) cells and the susceptibility of the neoplastic cells to both allogeneic and autologous LAK effectors were studied in B and T chronic lymphoproliferative disorders. While in B-cell chronic lymphocytic leukemia (B-CLL) the depressed natural killer function could be restored after a 7-day incubation with recombinant interleukin (IL-2), B-CLL mononuclear cells showed a reduced LAK activity compared with normal LAK cells. Furthermore, in all but 1 of the 20 B-CLL samples tested the leukemic cells were totally resistant to autologous LAK effectors. In most cases the leukemic cells were also resistant to normal allogeneic LAK cells. Competition experiments demonstrated that the patients' LAK cells, as well as normal LAK effectors, were capable of recognizing B-CLL cells, pointing, therefore, to a postbinding cytolytic defect. In hairy cell leukemia (HCL) an overall reduced LAK activity against allogeneic targets was documented, but, at variance from B-CLL, hairy cells were often susceptible to the lytic effect of normal LAK cells, and in half of the cases tested the neoplastic population was also sensitive in an autologous system. Similarly to B-CLL, in the great majority of T chronic lymphoproliferative disorders studied, the pathologic cells were resistant to normal and autologous LAK effectors and a defective LAK generation was found. These results demonstrate that in most B and T chronic leukemias the LAK function is defective and, when inducible, does not appear directed against the leukemic population. The possibility of exploiting an immunotherapeutic approach with IL-2/LAK cells in the management of chronic lymphoproliferative disorders does not gain support by these findings.
在B和T慢性淋巴细胞增殖性疾病中，研究了产生淋巴因子激活的杀伤（LAK）细胞的能力以及肿瘤细胞对同种异体和自体LAK效应细胞的敏感性。在B细胞慢性淋巴细胞白血病（B-CLL）中，与重组白细胞介素（IL-2）孵育7天后，降低的自然杀伤功能可恢复，但与正常LAK细胞相比，B-CLL单核细胞的LAK活性降低。此外，在测试的20个B-CLL样本中，除1个外，白血病细胞对自体LAK效应细胞完全耐药。在大多数情况下，白血病细胞对正常同种异体LAK细胞也耐药。竞争实验表明，患者的LAK细胞以及正常LAK效应细胞能够识别B-CLL细胞，因此表明存在结合后溶细胞缺陷。在毛细胞白血病（HCL）中，记录到针对同种异体靶标的总体LAK活性降低，但与B-CLL不同，毛细胞通常对正常LAK细胞的裂解作用敏感，并且在一半的测试病例中，肿瘤细胞群体在自体系统中也敏感。与B-CLL类似，在大多数研究的T慢性淋巴细胞增殖性疾病中，病理细胞对正常和自体LAK效应细胞耐药，并且发现LAK生成存在缺陷。这些结果表明，在大多数B和T慢性白血病中，LAK功能存在缺陷，并且在可诱导时，似乎并不针对白血病细胞群体。这些发现不支持在慢性淋巴细胞增殖性疾病的治疗中利用IL-2/LAK细胞进行免疫治疗的可能性。
