Hersey P, Bindon C, Edwards A, Murray E, Phillips G, McCarthy W H
Int J Cancer. 1981 Dec;28(6):695-703. doi: 10.1002/ijc.2910280607.
The influence of interleukin 2(IL2) on the cytotoxic activity of lymphocytes from patients with melanoma against autologous and a variety of allogeneic melanoma cells was studied. IL2 was produced from blood lymphocytes cultured for 24 h with phytohaemagglutinin (PHA) and purified by membrane chromatography to exclude PHA. Lymphocytes from 13 patients with melanoma at various clinical stages were cultured fro 6 days with IL2 (2 U/ml) and then tested for cytotoxic activity against autologous melanoma cells, three allogeneic melanoma and three non-melanoma cells. Autologous cytotoxicity was generated by culture with IL2 alone and was not increased by culture with both IL2 and autologous tumour cells. Marked increases in cytotoxic activity were also generated against the allogeneic target cells and were maximal against the NK-insensitive Chang target cells. Similar degrees of cytotoxicity were induced by IL2 stimulation of lymphocytes from melanoma patients, patients with nonmelanoma carcinoma and normal subjects against the allogeneic target cells. Cold target inhibition studies were carried out against IL2 induced autologous cytotoxicity in five patients. In four of five studies the autologous target cells inhibited more than the allogeneic target cells. There was no significant difference between the inhibition produced by allogeneic melanoma cells and that produced by non-melanoma cells. Similarly, in studies against allogeneic target cells, there was no significant difference in the inhibition produced by allogeneic melanoma compared to non-melanoma target cells. This applied irrespective of whether effector cells were from melanoma or non-melanoma subjects. These results suggest that lymphocytes from patients with melanoma are primed against autologous antigens in vivo and that provision of a second signal, IL2, in vitro can induce cytotoxicity against the autologous tumour. The cytotoxicity generated against the allogeneic target cells did not appear to have specificity to melanoma. Several results, such as the pattern of cytotoxicity against the target cells and change in cell surface markers on the lymphocytes during culture, suggested that cytotoxicity was mediated by activated T cells rather than by nature killer cells. These findings appear to have important implications both in the understanding of tumor host relationships and for the use of IL2 in therapy.
研究了白细胞介素2（IL2）对黑色素瘤患者淋巴细胞针对自体及多种异体黑色素瘤细胞的细胞毒活性的影响。IL2由用植物血凝素（PHA）培养24小时的血液淋巴细胞产生，并通过膜层析纯化以去除PHA。13例处于不同临床阶段的黑色素瘤患者的淋巴细胞用IL2（2 U/ml）培养6天，然后检测其针对自体黑色素瘤细胞、三种异体黑色素瘤细胞和三种非黑色素瘤细胞的细胞毒活性。单独用IL2培养可产生自体细胞毒性，同时用IL2和自体肿瘤细胞培养并不会增强这种毒性。针对异体靶细胞也产生了明显增强的细胞毒活性，对NK不敏感的Chang靶细胞的活性最强。IL2刺激黑色素瘤患者、非黑色素瘤癌患者及正常受试者的淋巴细胞针对异体靶细胞产生的细胞毒性程度相似。对5例患者进行了冷靶抑制研究，以检测IL2诱导的自体细胞毒性。在5项研究中的4项中，自体靶细胞的抑制作用超过异体靶细胞。异体黑色素瘤细胞产生的抑制作用与非黑色素瘤细胞产生的抑制作用之间无显著差异。同样，在针对异体靶细胞的研究中，异体黑色素瘤细胞与非黑色素瘤靶细胞产生的抑制作用也无显著差异。无论效应细胞来自黑色素瘤患者还是非黑色素瘤患者，均是如此。这些结果表明，黑色素瘤患者的淋巴细胞在体内已针对自体抗原致敏，在体外提供第二个信号IL2可诱导针对自体肿瘤的细胞毒性。针对异体靶细胞产生的细胞毒性似乎对黑色素瘤无特异性。一些结果，如针对靶细胞的细胞毒性模式以及培养过程中淋巴细胞表面标志物的变化，提示细胞毒性是由活化的T细胞而非自然杀伤细胞介导的。这些发现对于理解肿瘤与宿主的关系以及IL2在治疗中的应用似乎都具有重要意义。
