Kuss I, Saito T, Johnson J T, Whiteside T L
University of Pittsburgh Cancer Institute, Pennsylvania 15213-2582, USA.
Clin Cancer Res. 1999 Feb;5(2):329-34.
Patients with squamous cell carcinoma of the head and neck (SCCHN) frequently have impaired immune responses. Alterations in T-cell receptor-associated signaling molecules in tumor-infiltrating as well as circulating lymphocytes have been reported in these patients. Using quantitative flow cytometry analysis, we have demonstrated that expression of the zeta chain is significantly decreased relative to normal controls in both CD8+ and CD4+ T cells as well as CD3- CD56+ CD16+ natural killer cells in the peripheral blood of patients with SCCHN who, as a result of previous therapies, have no evident disease. Patients with a more aggressive type of SCCHN and those who experienced a recurrence or had a second primary cancer within the last 2 years of the study had the lowest zeta chain expression. In addition, SCCHN patients showed a significantly greater spontaneous ex vivo apoptosis, as measured by a terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay, in PBMCs, compared to normal controls. The observed decreased expression of zeta in T and natural killer cells coincided but did not directly correlate with significantly increased spontaneous apoptosis of lymphocytes obtained from treated patients with no evident disease. The results suggest that in patients with SCCHN, zeta chain defects and lymphocyte apoptosis are manifestations of long-lasting negative effects of tumor on the immune system.
头颈部鳞状细胞癌（SCCHN）患者的免疫反应常常受损。据报道，这些患者肿瘤浸润淋巴细胞以及循环淋巴细胞中与T细胞受体相关的信号分子存在改变。通过定量流式细胞术分析，我们发现，在既往接受过治疗且无明显疾病的SCCHN患者外周血中，相对于正常对照，CD8⁺和CD4⁺ T细胞以及CD3⁻ CD56⁺ CD16⁺自然杀伤细胞中的ζ链表达均显著降低。在研究的最后2年内，患有侵袭性更强的SCCHN类型的患者以及经历复发或患有第二原发性癌症的患者，其ζ链表达最低。此外，与正常对照相比，通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法检测发现，SCCHN患者外周血单个核细胞（PBMCs）的体外自发凋亡显著增加。在无明显疾病的接受治疗的患者中，观察到的T细胞和自然杀伤细胞中ζ链表达降低与淋巴细胞自发凋亡显著增加同时出现，但二者并无直接关联。结果表明，在SCCHN患者中，ζ链缺陷和淋巴细胞凋亡是肿瘤对免疫系统长期负面影响的表现。
