Snyderman C H, Heo D S, Johnson J T, D'Amico F, Barnes L, Whiteside T L
Department of Otolaryngology, University of Pittsburgh School of Medicine.
Arch Otolaryngol Head Neck Surg. 1991 Aug;117(8):899-905. doi: 10.1001/archotol.1991.01870200093016.
We compared the phenotype and antitumor effector function of lymphocytes obtained from tumor tissues, lymph nodes, and the peripheral blood of patients with head and neck cancer. Freshly isolated tumor-infiltrating lymphocytes were deficient in CD4+ T cells in comparison with lymph node lymphocytes (LNL) and peripheral blood lymphocytes. A significantly higher CD4/CD8 ratio observed in LNL vs tumor-infiltrating lymphocytes and peripheral blood lymphocytes was attributable to both a significant enrichment in CD4+ T cells as well as a decrease in CD8+ T cells. The percentage of natural killer cells (CD3-CD56+) was uniformly low in both tumor-infiltrating lymphocytes and LNL. In patients with cervical metastases, LNL contained an increased proportion of CD16+ cells. Tumor-involved lymph nodes were not enriched in the CD8+C11b+ subset of T "suppressor" lymphocytes compared with uninvolved lymph nodes. Also, tumor-involved lymph nodes had significantly fewer CD4+ T cells than did uninvolved lymph nodes. In comparison with peripheral blood lymphocytes, freshly isolated tumor-infiltrating lymphocytes and LNL were depleted of cytotoxic effector cells, as indicated by low or absent cytotoxic activity against tumor cell targets. The ability to generate lymphokine-activated killer cells was significantly reduced in LNL in comparison with peripheral blood lymphocytes. In patients with head and neck cancer, depressed local and regional antitumor responses are associated with a deficiency of functional cytotoxic effector cells rather than an increase in suppressor T lymphocytes.
我们比较了从头颈癌患者的肿瘤组织、淋巴结和外周血中获取的淋巴细胞的表型和抗肿瘤效应功能。与淋巴结淋巴细胞(LNL)和外周血淋巴细胞相比,新鲜分离的肿瘤浸润淋巴细胞中CD4+ T细胞缺乏。在LNL中观察到的CD4/CD8比值显著高于肿瘤浸润淋巴细胞和外周血淋巴细胞,这归因于CD4+ T细胞的显著富集以及CD8+ T细胞的减少。肿瘤浸润淋巴细胞和LNL中自然杀伤细胞(CD3-CD56+)的百分比均一致较低。在有颈部转移的患者中,LNL中CD16+细胞的比例增加。与未受累淋巴结相比,肿瘤累及的淋巴结中T“抑制”淋巴细胞的CD8+C11b+亚群未富集。此外,肿瘤累及的淋巴结中的CD4+ T细胞明显少于未受累淋巴结。与外周血淋巴细胞相比,新鲜分离的肿瘤浸润淋巴细胞和LNL中细胞毒性效应细胞减少,这表现为对肿瘤细胞靶标的细胞毒性活性较低或不存在。与外周血淋巴细胞相比,LNL中产生淋巴因子激活的杀伤细胞的能力显著降低。在头颈癌患者中,局部和区域抗肿瘤反应低下与功能性细胞毒性效应细胞缺乏有关,而非抑制性T淋巴细胞增加。