ALTERATIONS IN SIGNAL TRANSDUCTION MOLECULES IN LYMPHOCYTES-T FROM TUMOR-BEARING MICE
ALTERATIONS IN SIGNAL TRANSDUCTION MOLECULES IN LYMPHOCYTES-T FROM TUMOR-BEARING MICE
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DOI：
10.1126/science.1465616
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发表时间：
1992-12-11
期刊：
影响因子：
56.9
通讯作者：
OCHOA, AC
中科院分区：
文献类型：
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作者：
MIZOGUCHI, H;O'SHEA, JJ;OCHOA, AC
免疫反应受损经常发生在癌症患者或荷瘤小鼠中，但肿瘤引起的免疫缺陷的机制仍知之甚少。在体内小鼠结肠癌模型 (MCA-38) 中，荷瘤时间超过 26 天的动物会发育出细胞毒性功能受损的 CD8+ T 细胞，肿瘤坏死因子-α 和颗粒酶 B 基因的表达降低，体内介导抗肿瘤反应的能力降低。来自荷瘤小鼠的 T 淋巴细胞表达含有少量 CD3gamma 且完全缺乏 CD3zeta 的 T 细胞抗原受体，并被 Fc(ε) γ 链取代。酪氨酸激酶 p56lck 和 p59fyn 的表达也降低。这些变化可能是荷瘤宿主免疫缺陷的基础。
Impaired immune responses occur frequently in cancer patients or in tumor-bearing mice, but the mechanisms of the tumor-induced immune defects remain poorly understood. In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8+ T cells with impaired cytotoxic function, decreased expression of the tumor necrosis factor-alpha and granzyme B genes, and decreased ability to mediate an antitumor response in vivo. T lymphocytes from tumor-bearing mice expressed T cell antigen receptors that contained low amounts of CD3gamma and completely lacked CD3zeta, which was replaced by the Fc(epsilon) gamma-chain. Expression of the tyrosine kinases p56lck and p59fyn was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts.