Clayman G L, Taylor D L, Liu F J, Lavedan P, Savage H E, Schantz S P
Department of Head and Neck Surgery, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Laryngoscope. 1993 Mar;103(3):299-307. doi: 10.1288/00005537-199303000-00010.
An understanding of the role that immunomodulatory factors play in the effector phase of lymphokine-activated killer (LAK) activity is essential for the development of biologic response modifiers for use in the treatment of advanced carcinoma. Fifteen head and neck cancer patients were studied. Single-donor killer cells activated by recombinant interleukin-2 (10 U/mL) and induced in either a complete medium or complete medium plus a 10% autologous serum solution were used. Effector phase solutions of 25% autologous serum were used in chromium 51 release assays to determine sera immunomodulation of LAK cell cytotoxicity. Both K562 and squamous carcinoma (MDA686-Ln) tumor cell lines were tested. Significant effector phase inhibition (EPI) of cytotoxicity occurred in 40% of studied patients. Seventy percent of patients with stage III or IV or recurrent disease exhibited EPI, whereas only 20% of patients with stage I or II disease and 30% of controls did so. EPI of cancer patient serum correlated directly with alpha 1-antitrypsin, alpha 1-acid glycoprotein, and C-reactive protein (CRP) levels (MDA686-Ln targets) (r = 0.6, 0.7, and 0.6, respectively) (P < .02). Neither EPI against K562 targets nor EPI in control patients correlated with acute phase protein levels. These findings suggest that advances in in vivo immunomodulatory therapy will be dependent upon further elucidation of serologic inhibition of the effector phase of the LAK cell phenomenon. The relationship between LAK cell recognition and EPI requires further investigation.
了解免疫调节因子在淋巴因子激活的杀伤细胞（LAK）活性效应阶段所起的作用，对于开发用于治疗晚期癌症的生物反应调节剂至关重要。对15例头颈癌患者进行了研究。使用经重组白细胞介素-2（10 U/mL）激活并在完全培养基或完全培养基加10%自体血清溶液中诱导的单供体杀伤细胞。在铬51释放试验中使用含25%自体血清的效应阶段溶液，以确定血清对LAK细胞细胞毒性的免疫调节作用。对K562和鳞状癌细胞系（MDA686-Ln）均进行了检测。40%的研究患者出现了细胞毒性的显著效应阶段抑制（EPI）。III期或IV期或复发性疾病患者中有70%出现EPI，而I期或II期疾病患者中只有20%，对照组中有30%出现EPI。癌症患者血清的EPI与α1-抗胰蛋白酶、α1-酸性糖蛋白和C反应蛋白（CRP）水平直接相关（以MDA686-Ln为靶细胞）（r分别为0.6、0.7和0.6）（P<0.02）。针对K562靶细胞的EPI以及对照组患者的EPI均与急性期蛋白水平无关。这些发现表明，体内免疫调节治疗的进展将取决于对LAK细胞现象效应阶段血清学抑制作用的进一步阐明。LAK细胞识别与EPI之间的关系需要进一步研究。
