Wanebo H J, Blackinton D, Kouttab N, Mehta S
Department of Surgery, Roger Williams Medical Center, Providence, Rhode Island 02825.
Am J Surg. 1993 Oct;166(4):389-94. doi: 10.1016/s0002-9610(05)80339-3.
The immune system of patients with head and neck cancer is frequently depressed. Serum inhibitory factors and immune cell dysfunction are known contributors to this depression, but their relative roles are unclear. We have examined these factors to determine whether a common pathway is involved. Is the defect an unresponding "switched-off cell" or is it a remedial defect responsive to the removal of serum inhibitory factors and/or to lymphokine restoration? Immune tests were performed in 66 patients with high-stage head and neck cancer. Serum inhibitory factors were measured by incubation of heat-inactivated serum (10%) with phytohemagglutinin (PHA)-stimulated lymphocytes or natural killer (NK) cells using the K562 assay. Lymphokine-activated killer (LAK) cell cytotoxicity was measured (in the presence/absence of serum) using chromium 51-labeled Raji tumor cells cultured 5 days with interleukin-2 (IL-2) (100 or 1,000 U/mL) and/or interferon-alpha (INF-alpha) (100 U/mL). IL-2 receptors, CD25 or p55 (low affinity) and p75 (high affinity), were measured by flow cytometry through fluorescence-activated cell sorter analysis. Serum inhibitory factors were detected in more than 50% of the patients. Head and neck cancer sera significantly inhibiting the normal lymphocyte response to PHA (11 of 22 patients), as well as significantly inhibiting the NK response of normal lymphocytes and the functional expression of the IL-2 receptor. LAK cell function at low-dose IL-2 was depressed in 45% of the patients (9 of 20) and was restored by increased IL-2 (1,000 U/mL) or a combination of IL-2 and INF-alpha. Twenty-five percent of the patients were unresponsive to maximum lymphokine stimulation. Half of the patients had depressed expression of the low-affinity IL-2 receptor (CD25). The cause of immune depression in patients with head and neck cancer is multifactorial and is related to serum inhibitory factors, as well as to inherent cellular defects. Based on these data, we would suggest a therapeutic approach in selected patients that includes the removal of serum inhibitory factors by plasmapheresis and restoration of cellular defects by combined IL-2 with or without INF-alpha.
头颈癌患者的免疫系统常常受到抑制。血清抑制因子和免疫细胞功能障碍是导致这种抑制的已知因素，但其相对作用尚不清楚。我们研究了这些因素，以确定是否涉及共同途径。这种缺陷是无反应的“关闭细胞”，还是对去除血清抑制因子和/或恢复淋巴因子有反应的补救性缺陷？对66例晚期头颈癌患者进行了免疫测试。通过使用K562检测法，将热灭活血清（10%）与植物血凝素（PHA）刺激的淋巴细胞或自然杀伤（NK）细胞孵育来测量血清抑制因子。使用用白细胞介素-2（IL-2）（100或1000 U/mL）和/或干扰素-α（INF-α）（100 U/mL）培养5天的51铬标记的Raji肿瘤细胞，测量（在有/无血清的情况下）淋巴因子激活的杀伤（LAK）细胞的细胞毒性。通过荧光激活细胞分选分析，用流式细胞术测量IL-2受体、CD25或p55（低亲和力）和p75（高亲和力）。超过50%的患者检测到血清抑制因子。头颈癌血清显著抑制正常淋巴细胞对PHA的反应（22例患者中的11例），以及显著抑制正常淋巴细胞的NK反应和IL-2受体的功能表达。45%的患者（20例中的9例）在低剂量IL-2时LAK细胞功能受到抑制，并通过增加IL-2（1000 U/mL）或IL-2与INF-α的组合得以恢复。25%的患者对最大淋巴因子刺激无反应。一半的患者低亲和力IL-2受体（CD25）表达降低。头颈癌患者免疫抑制的原因是多因素的，与血清抑制因子以及固有细胞缺陷有关。基于这些数据，我们建议对选定患者采取一种治疗方法，包括通过血浆置换去除血清抑制因子，并通过联合使用IL-2加或不加INF-α来恢复细胞缺陷。
