Allavena P, Introna M, Sessa C, Mangioni C, Mantovani A
J Natl Cancer Inst. 1982 Apr;68(4):555-62.
A study was done to investigate the tumoricidal activity of peripheral blood lymphocytes (PBL) and tumor-associated lymphoid cells (TAL) against freshly isolated tumor cells in human ovarian carcinoma. TAL and carcinoma cells were purified by density and velocity sedimentation on discontinuous Ficoll-Hypaque gradients and fetal bovine serum. Purified carcinoma cells from 23 ascitic and 3 solid tumors were used as targets in a 4- or a 20-hour 51Cr release assay. K562 cells were used to measure natural killer (NK) activity. Freshly purified ovarian carcinoma cells were relatively resistant to lysis by normal unstimulated PBL. Cytolytic activity of ovarian cancer PBL and TAL did not exceed that of control PBL: Only one PBL preparation had high levels of cytotoxicity (36.2 and 42.9% specific lysis after 4 and 20 hr at an effector-to-target cell ratio of 50:1) against autologous cancer cells but not against allogeneic targets (less than 5% specific lysis). TAL and, to a lesser extent, ovarian cancer PBL showed impaired NK activity against K562 compared to the activity seen in controls. In vitro exposure to partially purified human fibroblast interferon (IFN) (1,000 U/ml for 1-18 hr) augmented NK activity against K562 of PBL and TAL. When ovarian carcinoma cells were used as targets, IFN enhanced the cytotoxicity of normal PBL in a 4- and 20-hour assay; stimulation by IFN was less frequently observed with ovarian cancer PBL and TAL in a 4-hour assay, but after 20 hours effector cells from tumor-bearing subjects showed IFN-boosted cytotoxicity against carcinoma cells similar to the degree of cytotoxicity seen in controls. IFN enhanced the cytotoxicity of PBL and TAL against both autologous and allogeneic carcinoma cells. Thus PBL and TAL are rarely cytotoxic against 51Cr-labeled fresh autologous carcinoma cells, but in vitro exposure to IFN induced low levels of killing of ovarian tumor cells.
一项研究旨在调查外周血淋巴细胞(PBL)和肿瘤相关淋巴细胞(TAL)对人卵巢癌新鲜分离肿瘤细胞的杀瘤活性。通过在不连续的Ficoll-泛影葡胺梯度和胎牛血清上进行密度和速度沉降来纯化TAL和癌细胞。来自23例腹水肿瘤和3例实体肿瘤的纯化癌细胞在4小时或20小时的51Cr释放试验中用作靶细胞。K562细胞用于测量自然杀伤(NK)活性。新鲜纯化的卵巢癌细胞对正常未刺激的PBL裂解相对抗性。卵巢癌PBL和TAL的细胞溶解活性不超过对照PBL:只有一种PBL制剂对自体癌细胞具有高水平的细胞毒性(在效应细胞与靶细胞比例为50:1时,4小时和20小时后特异性裂解分别为36.2%和42.9%),但对同种异体靶细胞无细胞毒性(特异性裂解小于5%)。与对照相比,TAL以及在较小程度上卵巢癌PBL对K562的NK活性受损。体外暴露于部分纯化的人成纤维细胞干扰素(IFN)(1000 U/ml,1 - 18小时)可增强PBL和TAL对K562的NK活性。当卵巢癌细胞用作靶细胞时,IFN在4小时和20小时试验中增强了正常PBL的细胞毒性;在4小时试验中,卵巢癌PBL和TAL较少观察到IFN的刺激作用,但20小时后,荷瘤受试者的效应细胞对癌细胞显示出与对照中所见细胞毒性程度相似的IFN增强的细胞毒性。IFN增强了PBL和TAL对自体和同种异体癌细胞的细胞毒性。因此,PBL和TAL对51Cr标记的新鲜自体癌细胞很少具有细胞毒性,但体外暴露于IFN可诱导对卵巢肿瘤细胞的低水平杀伤。