Shiiba K, Suzuki R, Kawakami K, Ohuchi A, Kumagai K
Cancer Immunol Immunother. 1986;21(2):119-28. doi: 10.1007/BF00199859.
The generation of lymphokine activated killer (LAK) cells by recombinant IL2 (rIL2) in collaboration with interferon gamma (IFN gamma) was examined in peripheral blood mononuclear cells (PBMC) from patients with malignant tumors of the digestive organs and breast cancer. LAK cytotoxicity could be induced by rIL2 at 10 units/ml in 10 of 12 patients and 20 of 37 using fresh autologous tumor cells and PK-1, an established solid tumor cell line as a target, respectively. Among 34 patients, in which titers of IFN gamma produced were assayed, 12 showed no IFN gamma production. All of these 12 patients had no or extremely low LAK activity, suggesting the correlation of LAK generation with the production of IFN gamma in response to rIL2. LAK induction by rIL2 in PBMC of cancer patients was almost completely inhibited by addition of anti-IFN gamma serum. Depressed LAK generation, which was accompanied by no or low levels of IFN gamma production, was partially restored by addition of exogenous recombinant IFN gamma. These results indicate that LAK induction by rIL2 in cancer patients involves the production of IFN gamma and its interaction with rIL2. The results also suggested the presence of a factor(s) suppressing LAK induction by rIL2 in the serum of cancer patients. Based on these results, the cancer patients could be divided into the following three groups. Group 1, in which the serum suppressor activity was undetectable, had the same level of LAK cytotoxicity in PBMC as healthy controls. Group 2 showed the serum suppressor factor and had the lower level of cytotoxicity in PBMC when cultivated in autologous serum (AS) compared to healthy controls. The depressed LAK induction in AS medium was restored to a normal level in culture with fetal calf serum (FCS) plus rIL2, or by addition of rIFN gamma, or high concentrations of rIL2 in AS medium. The last group (group 3), in which the serum suppressor factor was also found, had the lowest level of cytotoxicity compared to healthy controls. The LAK induction in these patients could not be restored to a normal level by culture in FCS medium, addition of exogenous rIFN gamma or high concentrations of rIL2, suggesting the possibility that the deficit of LAK generation in this group might involve the dysfunction or the lack of IL2 responder cells, in addition to the presence of a serum suppressor factor(s).
我们研究了重组白细胞介素2（rIL2）与干扰素γ（IFNγ）协同作用在外周血单个核细胞（PBMC）中产生淋巴因子激活的杀伤细胞（LAK）的情况，这些外周血单个核细胞来自患有消化器官恶性肿瘤和乳腺癌的患者。分别使用新鲜的自体肿瘤细胞和已建立的实体瘤细胞系PK - 1作为靶细胞，12例患者中有10例以及37例患者中有20例在rIL2浓度为10单位/毫升时可诱导出LAK细胞毒性。在检测了IFNγ产生滴度的34例患者中，有12例未检测到IFNγ产生。这12例患者均无或仅有极低的LAK活性，提示LAK细胞的产生与对rIL2反应中IFNγ的产生相关。在癌症患者的PBMC中，加入抗IFNγ血清几乎完全抑制了rIL2诱导的LAK细胞产生。加入外源性重组IFNγ可部分恢复伴有无或低水平IFNγ产生的LAK细胞产生受抑制的情况。这些结果表明，癌症患者中rIL2诱导LAK细胞产生涉及IFNγ的产生及其与rIL2的相互作用。结果还提示癌症患者血清中存在抑制rIL2诱导LAK细胞产生的一种或多种因子。基于这些结果，癌症患者可分为以下三组。第1组血清中未检测到抑制活性，其PBMC中的LAK细胞毒性水平与健康对照相同。第2组存在血清抑制因子，与健康对照相比，在自体血清（AS）中培养时PBMC中的细胞毒性水平较低。在含有胎牛血清（FCS）加rIL2的培养基中培养、加入rIFNγ或在AS培养基中加入高浓度rIL2后，AS培养基中受抑制的LAK细胞诱导可恢复到正常水平。最后一组（第3组）也发现了血清抑制因子，与健康对照相比其细胞毒性水平最低。在这些患者中，通过在FCS培养基中培养、加入外源性rIFNγ或高浓度rIL2，LAK细胞诱导不能恢复到正常水平，这提示该组中LAK细胞产生不足除了存在血清抑制因子外，可能还涉及IL2反应细胞功能障碍或缺乏。
