Hadden J W
Department of Internal Medicine, University of South Florida College of Medicine, Tampa 33612, USA.
Int J Immunopharmacol. 1997 Nov-Dec;19(11-12):629-44. doi: 10.1016/s0192-0561(97)00063-5.
Patients with head and neck squamous cell cancer have cell-mediated immune defects and anergy, which progress with disease. T-lymphocytopenia and dysfunction, monocyte dysfunction, prostaglandins, antigen-antibody complexes, serum and cell suppressive factors, radiation therapy and poor nutrition with zinc deficiency all contribute. Nevertheless, cell-mediated immunoreactivity to tumor is manifest in the majority of the patient's blood and regional nodes, and in the tumor itself by tumor-infiltrating lymphocytes. Lymphocytes from these sources cloned in the presence of interleukin-2 +/- tumor extracts show relatively specific cytotoxicity against squamous cell cancer. Humoral immunity is intact, and increased IgA and IgE levels and antibodies reactive to tumor antigens are common. Tumor-associated antigens detected in serum and tumor include carcinoembryonic antigen, tumor polypeptide antigen, squamous cell cancer antigens, tumor antigen-4 and various mucin antigens. The mucin antigens, in particular, can elicit T-cell responses. Humoral reactivity to such antigens is manifest in circulating immune complexes and immunoglobulin coating of tumor surfaces. Immunotherapeutic efforts in head and neck squamous cell cancer should logically employ T-cell adjuvants, contrasuppression and immunorestoration. Non-specific stimulation with bacille Calmette-Guerin (BCG), levamisole and other agents has not been successful. Encouraging results have been observed in limited trials with indomethacin and plasmapheresis. Early trials with local administration of low dosages of interferon-alpha, natural interleukin-2 and a natural interleukin mixture have produced partial and complete regressions with no toxicity and with intense leukocyte infiltration indicating cellular immunity. Efforts are needed to define the mechanisms and the antigens involved in these reactions. On the contrary, treatments with high dosages of recombinant interferon-alpha and interleukin-2 have yielded few responses and considerable toxicity. Combination strategies are discussed which may improve upon these initial immunotherapeutic effects of these low dose trials.
头颈部鳞状细胞癌患者存在细胞介导的免疫缺陷和无反应性，且会随疾病进展。T淋巴细胞减少和功能障碍、单核细胞功能障碍、前列腺素、抗原 - 抗体复合物、血清和细胞抑制因子、放射治疗以及伴有锌缺乏的营养不良均有影响。然而，大多数患者的血液、区域淋巴结以及肿瘤本身通过肿瘤浸润淋巴细胞表现出对肿瘤的细胞介导免疫反应性。在白细胞介素 -2 ± 肿瘤提取物存在的情况下克隆自这些来源的淋巴细胞对鳞状细胞癌显示出相对特异性的细胞毒性。体液免疫是完整的，IgA和IgE水平升高以及对肿瘤抗原具有反应性的抗体很常见。在血清和肿瘤中检测到的肿瘤相关抗原包括癌胚抗原、肿瘤多肽抗原、鳞状细胞癌抗原、肿瘤抗原 -4以及各种粘蛋白抗原。特别是粘蛋白抗原可引发T细胞反应。对这类抗原的体液反应性表现为循环免疫复合物以及肿瘤表面的免疫球蛋白包被。对头颈部鳞状细胞癌的免疫治疗应合理采用T细胞佐剂、抗抑制和免疫恢复方法。用卡介苗（BCG）、左旋咪唑和其他药物进行的非特异性刺激未获成功。在吲哚美辛和血浆置换的有限试验中观察到了令人鼓舞的结果。早期局部给予低剂量干扰素 -α、天然白细胞介素 -2和天然白细胞介素混合物的试验已产生部分和完全缓解且无毒性，并有强烈的白细胞浸润表明存在细胞免疫。需要努力确定这些反应所涉及的机制和抗原。相反，高剂量重组干扰素 -α和白细胞介素 -2治疗产生的反应很少且毒性很大。讨论了联合策略，这可能会改善这些低剂量试验的初始免疫治疗效果。
