Bugis S P, Lotzová E, Savage H E, Hester J P, Racz T, Sacks P G, Schantz S P
Department of Surgery, Queen's University, Kingston, Ontario.
Cancer Immunol Immunother. 1990;31(3):176-81. doi: 10.1007/BF01744733.
Cytolytic activation of peripheral blood lymphocytes by recombinant interleukin-2 (rIL-2) in patients with squamous cell carcinoma (SCC) of the head and neck may be inhibited by serum blocking factors, and this could influence therapeutic efficacy. Peripheral blood lymphocytes from 21 patients with this disease and 17 controls were incubated with 10-1000 U rIL-2 for 6 days in supplemented complete medium (containing 10% fetal calf serum) or the same medium plus 10% autologous serum. After washing the effector cells, we determined their cytotoxicity against K562 and MDA1386, a lymphokine-activated-killer(LAK)-sensitive SCC cell line, using a 51Cr-release assay. Patient sera inhibited LAK-generated lysis of both MDA1386 and K562, while control sera from healthy persons inhibited LAK-generated lysis of MDA1386. The blocking activity of patient sera tended to be greater than that of control sera. The sera of patients with untreated or recurrent disease and those who were free of disease had equivalent inhibitory capacity. The serum blocking factor acted in a dose-dependent manner, and inhibition was overcome by increasing the dose of rIL-2. Levels of circulating immune complexes (measured by the C1q binding method) did not correlate significantly with inhibition. A clinical protocol of repeated plasma exchange in patients with advanced and recurrent squamous cell carcinoma of the head and neck allowed sequential study of one patients's serum before, during, and after treatments. Plasmapheresis removed serum inhibitory factors, albeit temporarily. The activity of serum blocking factors in patients with this disease can be modulated by increasing doses of rIL-2 and by plasma exchange. This modulation may be important to improving clinical response rates for patients undergoing immunotherapy.
头颈部鳞状细胞癌（SCC）患者外周血淋巴细胞被重组白细胞介素-2（rIL-2）进行细胞溶解激活的过程可能会受到血清阻断因子的抑制，而这可能会影响治疗效果。将21例该疾病患者及17名对照者的外周血淋巴细胞在补充的完全培养基（含10%胎牛血清）或相同培养基加10%自体血清中与10 - 1000 U rIL-2孵育6天。洗涤效应细胞后，我们使用51Cr释放试验测定其对K562和MDA1386（一种对淋巴因子激活的杀伤细胞[LAK]敏感的SCC细胞系）的细胞毒性。患者血清抑制了LAK对MDA1386和K562的杀伤作用，而健康人的对照血清仅抑制LAK对MDA1386的杀伤作用。患者血清的阻断活性往往高于对照血清。未经治疗或复发疾病患者以及无疾病患者的血清具有同等的抑制能力。血清阻断因子呈剂量依赖性作用，增加rIL-2剂量可克服抑制作用。循环免疫复合物水平（通过C1q结合法测定）与抑制作用无显著相关性。对头颈部晚期和复发性鳞状细胞癌患者进行重复血浆置换的临床方案，使得能够对一名患者治疗前、治疗期间和治疗后的血清进行序贯研究。血浆置换去除了血清抑制因子，尽管只是暂时的。增加rIL-2剂量和进行血浆置换可调节该疾病患者血清阻断因子的活性。这种调节对于提高接受免疫治疗患者的临床反应率可能很重要。
