Loss of T-cell receptor zeta chain and p56lck in T-cells infiltrating human renal cell carcinoma.
Loss of T-cell receptor zeta chain and p56lck in T-cells infiltrating human renal cell carcinoma.
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发表时间：
1993-12
期刊：
影响因子：
11.2
通讯作者：
J. Finke;A. Zea;J. Stanley;D. Longo;H. Mizoguchi;R. Tubbs;R. Wiltrout;J. O’Shea;S. Kudoh
中科院分区：
文献类型：
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作者：
J. Finke;A. Zea;J. Stanley;D. Longo;H. Mizoguchi;R. Tubbs;R. Wiltrout;J. O’Shea;S. Kudoh
癌症患者和携带肿瘤的小鼠会出现进行性免疫抑制，表现为迟发型超敏反应降低、T细胞溶解活性降低、淋巴因子产生减少以及T细胞增殖反应降低。这些变化背后的机制尚不完全清楚。我们最近报告称，患有长期（28 天）肿瘤的小鼠的 T 细胞信号转导存在显着改变。我们假设肿瘤产生的可溶性产物或肿瘤免疫反应产生的可溶性产物可能是诱导 T 细胞发生变化的原因。这里测试的肾细胞癌患者的肿瘤浸润淋巴细胞显示，11 例中有 10 例 T 细胞受体 zeta 链和 p56lck 酪氨酸激酶的表达显着下降。肿瘤浸润淋巴细胞存在重大变化，而外周血白细胞 T 细胞仅发生微小变化，这支持了缺陷是由暴露于肿瘤而引起的观点。这些结果表明肿瘤浸润淋巴细胞在肾细胞癌患者中的抗肿瘤功效可能会受到损害。
Cancer patients and mice bearing tumors develop a progressive immunosuppression manifested by a decreased delayed-type hypersensitivity, decreased T-cell lytic activity, diminished production of lymphokines, and a reduced T-cell proliferative response. The mechanisms underlying these changes are incompletely understood. We recently reported the presence of marked alterations in signal transduction in T-cells from mice bearing long-term (28-day) tumours. We hypothesized that a soluble product produced by the tumor or resulting from the immune response to tumor might be responsible for inducing the changes in T-cells. Tumor-infiltrating lymphocytes from patients with renal cell carcinoma tested here showed, in 10 of 11 cases, a marked decrease in the expression of the T-cell receptor zeta chain and in p56lck tyrosine kinase. The presence of major alterations in the tumor-infiltrating lymphocytes with only minor changes in the peripheral blood leukocyte T-cells supports the notion that the defects are induced by exposure to tumor. These results suggest that tumor-infiltrating lymphocytes may be compromised in their antitumor efficacy in patients with renal cell cancer.