Brenner B G, McCrea E L, Margolese R G
Department of Surgical Oncology, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
Anticancer Res. 1988 Jul-Aug;8(4):653-8.
The cytotoxic capacity of resting, interleukin-2 (IL-2)-stimulated and in vitro cultured (3-5 days in 10 U/ml IL-2 containing media) peripheral blood lymphocytes (PBLs) from breast cancer patients to a panel of established mammary tumor cell lines was ascertained. Significant cytolysis (ranging from 7.8 to 12.4%, at an effector: target ratio of 20:1) of all mammary tumor targets (MCF-7, 734B, ZR-75-1, ZR-75-30, BT-20 and Hs578T) by PBLs was demonstrable in 18 h chromium release assays. Natural killer (NK) cytotoxicity was distinct from IL-2 stimulated (5 U/ml) and in vitro cultured PBL cytotoxicity in that resting PBLs were not cytolytic to RAJI cells, normal breast epithelia (Hs578Bst) and fibroblasts. Basal NK activity against mammary tumor targets was significantly reduced in patients receiving chemotherapy when compared to both untreated patients and normal controls. In criss-cross cold target inhibition studies, ZR-75-1 and K562 targets were not mutually competitive in NK cell assays (using resting PBLs) but were mutually competitive in lymphokine-activated killer (LAK) assays (using in vitro cultured PBLs). In eleven independent experiments, basal NK activity of ZR-75-1 cells was increased by a cold target excess of K562 (8.2 +/- 2.4% vs 30.5 +/- 5.2%, mean +/- SE, p greater than 0.01, cold:hot target ratio = 10:1). Interestingly, no such parallel increase of cytolysis of 734B targets by K562 cells was observed. Basal cytotoxicity against ZR-75-1 and K562 targets was serologically depleted using antibodies to natural killer cells HNK-1 and Leu 11b. Thus mammary tumor cell lines parallel autologous tumor cells, yet show features that are distinct from NK-resistant and sensitive lymphoid cell lines in their susceptibility to natural resistant cytolytic mechanisms.
测定了乳腺癌患者静息的、经白细胞介素-2（IL-2）刺激的以及体外培养的（在含10 U/ml IL-2的培养基中培养3 - 5天）外周血淋巴细胞（PBLs）对一组已建立的乳腺肿瘤细胞系的细胞毒性能力。在18小时的铬释放试验中，可证明所有乳腺肿瘤靶细胞（MCF-7、734B、ZR-75-1、ZR-75-30、BT-20和Hs578T）均有显著的细胞溶解（在效应细胞与靶细胞比例为20:1时，细胞溶解率在7.8%至12.4%之间）。自然杀伤（NK）细胞毒性与经IL-2刺激（5 U/ml）和体外培养的PBL细胞毒性不同，因为静息的PBLs对RAJI细胞、正常乳腺上皮细胞（Hs578Bst）和成纤维细胞无细胞溶解作用。与未治疗的患者和正常对照相比，接受化疗的患者对乳腺肿瘤靶细胞的基础NK活性显著降低。在交叉冷靶抑制研究中，ZR-75-1和K562靶细胞在NK细胞试验（使用静息PBLs）中不相互竞争，但在淋巴因子激活的杀伤细胞（LAK）试验（使用体外培养的PBLs）中相互竞争。在11项独立实验中，K562细胞冷靶过量使ZR-75-1细胞的基础NK活性增加（分别为8.2±2.4%和30.5±5.2%，平均值±标准误，p＞0.01，冷靶与热靶比例 = 10:1）。有趣的是，未观察到K562细胞对734B靶细胞的细胞溶解有类似的平行增加。使用抗自然杀伤细胞HNK-1和Leu 11b的抗体可血清学耗尽对ZR-75-1和K562靶细胞的基础细胞毒性。因此，乳腺肿瘤细胞系与自体肿瘤细胞相似，但在对自然抗性细胞溶解机制的敏感性方面表现出与NK抗性和敏感淋巴细胞系不同的特征。
