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首页> 外文OA文献 >Autologous tumor-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas. Activation by interleukin 2 and autologous tumor cells, and involvement of the T cell receptor
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Autologous tumor-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas. Activation by interleukin 2 and autologous tumor cells, and involvement of the T cell receptor

机译：在人类转移性黑色素瘤浸润中的自体肿瘤特异性细胞毒性T淋巴细胞。白细胞介素2和自体肿瘤细胞的激活以及T细胞受体的参与

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TIL from metastatic melanoma proliferated by greater than 1,000-fold (840-3,675, mean 1,543) after 6 wk in culture of mixtures of TIL and tumor cells with rIL-2 alone. Cytolysis was restricted to autologous tumor cells. CD8+ T cells were the predominant population of TIL before and after expansion, and were primarily responsible for autologous tumor-specific CTL activity. No other rIL-2-activated lymphocytes from peripheral blood, lymph nodes with melanoma metastasis, or TIL from sarcoma or renal cell carcinoma had autologous tumor-specific CTL activity. There were few or no CD16+ NK cells in TIL from metastatic melanoma before or after incubation with rIL-2, respectively. However, TIL from sarcoma or renal cell carcinoma contained a substantial proportion of CD3-CD16+ NK cells, which increased in number in culture with rIL-2. Purified CD16+ NK cells as well as CD3+CD16- T cells from rIL-2-activated TIL of renal cell carcinoma displayed MHC-nonrestricted cytotoxicity. At the clonal level as determined by limiting dilution, 8 of 10 clones from melanoma TIL displayed cytotoxicity restricted to autologous tumor cells, while all 13 clones from renal cancer TIL equally lysed autologous and allogeneic tumor cells. Anti-T cell receptor (TCR)-alpha/beta(WT31) mAb as well as anti-CD3 mAb inhibited autologous melanoma cell-specific CTL activity mediated by rIL-2- activated TIL at the effector phase. These two mAbs also inhibited rIL- 2-dependent proliferation of these TIL when added to the culture. Pretreatment of fresh melanoma cells with mAb to MHC antigens followed by washing inhibited specific CTL activity. These results suggest that both TCR-alpha/beta on effector TIL and MHC antigens on fresh tumor cells are involved in the specific immune-recognition. After reaching maximum propagation, TIL from metastatic melanoma responded poorly to rIL-2 alone. However, stimulation with fresh autologous melanoma cells restored both CTL activity and proliferation in response to rIL-2. The latter is associated with IL-2 receptor (Tac antigen) expression on the surface. These results indicate that TIL from metastatic melanomas may have unique characteristics different from lymphocytes obtained from the other sources, and may contain precursor CTL sensitized in vivo to autologous tumor cells, and thus can be propagated in larger numbers with rIL-2 alone while retaining autologous tumor-specific CTL activity.
机译：在仅用rIL-2的TIL和肿瘤细胞混合物培养6周后，来自转移性黑色素瘤的TIL增殖了1,000倍以上（840-3,675，平均1,543）。细胞溶解仅限于自体肿瘤细胞。 CD8 + T细胞是扩增前后TIL的主要群体，并且主要负责自体肿瘤特异性CTL活性。外周血，具有黑色素瘤转移的淋巴结，肉瘤或肾细胞癌的TIL中没有其他rIL-2激活的淋巴细胞具有自体肿瘤特异性CTL活性。在与rIL-2孵育之前或之后，来自转移性黑色素瘤的TIL中CD16 + NK细胞很少或没有。但是，来自肉瘤或肾细胞癌的TIL包含相当一部分CD3-CD16 + NK细胞，与rIL-2一起培养时其数量增加。从肾细胞癌的rIL-2激活的TIL纯化的CD16 + NK细胞以及CD3 + CD16- T细胞显示出MHC非限制性的细胞毒性。在通过有限稀释确定的克隆水平上，来自黑素瘤TIL的10个克隆中的8个显示出对自体肿瘤细胞的细胞毒性，而来自肾癌TIL的所有13个克隆均裂解了自体和同种异体肿瘤细胞。抗T细胞受体（TCR）-α/β（WT31）mAb以及抗CD3 mAb抑制了在效应期由rIL-2激活的TIL介导的自体黑素瘤细胞特异性CTL活性。当添加到培养物中时，这两个mAb也抑制了这些TIL的rIL-2依赖性增殖。用针对MHC抗原的mAb预处理新鲜的黑色素瘤细胞，然后洗涤，抑制了特定的CTL活性。这些结果表明，效应TIL上的TCR-α/β和新鲜肿瘤细胞上的MHC抗原均参与了特异性免疫识别。达到最大繁殖后，来自转移性黑色素瘤的TIL对单独的rIL-2的反应较差。然而，新鲜的自体黑素瘤细胞刺激恢复了CTL活性和对rIL-2的增殖。后者与表面上的IL-2受体（Tac抗原）表达有关。这些结果表明，来自转移性黑色素瘤的TIL可能具有与其他来源的淋巴细胞不同的独特特征，并且可能包含体内对自体肿瘤细胞敏化的前体CTL，因此可以单独使用rIL-2进行大量繁殖，同时保留自体肿瘤特异性CTL活性。

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