Pislarasu M, Oproiu A, Taranu D, Herberman R B, Sulica A
Department of Immunology, Babes Institute, Bucharest, Romania.
Cancer Res. 1988 May 1;48(9):2596-603.
As previously reported for natural killer (NK) cells of normal individuals, prior incubation of peripheral blood lymphocytes from cancer patients with human normal serum or monomeric immunoglobulin G reduced their subsequent capacity to kill K562 target cells in a 4-h 51Cr release assay. The NK activity of such treated effector cells was significantly inhibited only by 58% of sera from patients with colorectal adenocarcinoma (21 of 36 cases) and by 67% of sera from patients with other lymphoid or nonlymphoid solid tumors (22 of 33 cases). The cytotoxic activity of cells previously incubated with eight noninhibitory sera was even augmented relative to medium-treated peripheral blood lymphocytes (control). The 26 untreated cancer sera which did not inhibit significantly the NK activity (I-) always developed significant inhibitory capacity upon heating at 56 degrees C for 30 min (delta+). An additional seven (21%) patients with colorectal carcinoma and four (27%) patients with other cancers were identified as having type II NK regulation, defined as sera with untreated inhibitory capacity (I+) but with appreciably more inhibition after heating (delta+). The sera of the last group of patients with colorectal adenocarcinoma (14 of 36 cases) defined as having type III NK regulation were not different from control sera isolated from normal individuals (I+ delta-) except that they induced an inhibition greater than that caused by normal sera. The modulatory characteristics of sera from the first two categories of patients appear to be cancer associated, since the patterns I- delta+ or I+ delta+ were observed with sera from only one of 30 patients with benign digestive diseases and two of 100 apparently healthy individuals. Preliminary results of longitudinal investigations of patients with colorectal adenocarcinoma revealed also that these patterns disappeared several months after resection of their tumor in all five tested patients, whereas the type III NK regulation found in patients with poor prognostic factors was unchanged after surgery in the other five of six patients. The three different categories of cancer sera identified by the functional assay of NK regulation indicated differences among our group of patients which were not paralleled by differences in levels of cytotoxic reactivity of their NK cells assayed in vitro in the absence of autologous serum.(ABSTRACT TRUNCATED AT 400 WORDS)
正如之前关于正常个体自然杀伤(NK)细胞的报道,将癌症患者的外周血淋巴细胞预先与人正常血清或单体免疫球蛋白G孵育,会降低其随后在4小时51Cr释放试验中杀伤K562靶细胞的能力。在结直肠癌患者(36例中的21例)的血清中,此类处理过的效应细胞的NK活性仅被58%显著抑制,在其他淋巴或非淋巴实体瘤患者(33例中的22例)的血清中,被67%显著抑制。相对于用培养基处理的外周血淋巴细胞(对照),预先用八种无抑制作用的血清孵育的细胞的细胞毒性活性甚至增强。26份未显著抑制NK活性的未处理癌症血清(I-)在56℃加热30分钟后总是产生显著的抑制能力(δ+)。另外7例(21%)结直肠癌患者和4例(27%)其他癌症患者被确定具有II型NK调节,定义为血清具有未处理时的抑制能力(I+)但加热后抑制作用明显增强(δ+)。最后一组被定义为具有III型NK调节的结直肠癌患者(36例中的14例)的血清与从正常个体分离的对照血清(I+δ-)没有差异,只是它们诱导的抑制作用大于正常血清引起的抑制作用。前两类患者血清的调节特征似乎与癌症相关,因为在30例良性消化系统疾病患者中只有1例以及100例明显健康个体中只有2例的血清观察到I-δ+或I+δ+模式。对结直肠癌患者的纵向研究的初步结果还显示在所有五名接受测试的患者中,这些模式在肿瘤切除几个月后消失,而在另外六名患者中的五名患者中,具有不良预后因素的患者中发现的III型NK调节在手术后没有变化。通过NK调节功能测定确定的三类不同癌症血清表明我们的患者组之间存在差异,而在没有自体血清的情况下体外测定的NK细胞细胞毒性反应水平的差异与之并不平行。(摘要截断于400字)