Hedley S J, Murray A, Sisley K, Ghanem G, Morandini R, Gawkrodger D J, Mac Neil S
Division of Clinical Sciences, Northern General Hospital, Sheffield, UK.
Melanoma Res. 2000 Aug;10(4):323-30. doi: 10.1097/00008390-200008000-00003.
This study was undertaken to investigate whether alpha-melanocyte stimulating hormone (alphaMSH) influences the interaction of melanoma cells with T-lymphocytes in the light of previous work from our laboratories showing that alphaMSH can reduce tumour necrosis factor-alpha (TNFalpha) stimulated ICAM-1 upregulation in both normal and transformed melanocytes. Two cutaneous melanoma cell lines--A375-SM and HBL--were examined initially. A375-SM cells gave only a two-fold increase in T-cell proliferation, which was not much improved by the pretreatment of the melanoma cells with cytokines. HBL cells induced a three-fold increase in T-cell proliferation, which was slightly enhanced by the addition of cytokines. Neither cell line expressed B7(1), HBL cells expressed a low level of B7(2), whereas A375-SM cells had little, if any, B7(2) expression. Addition of alphaMSH reduced the interaction between these cutaneous melanoma cells and T-lymphocytes in some, but not all, conditions. An ocular melanoma cell line transfected with B7 showed a modest interaction with T-cells (in two out of three donors) and this response was reduced by the addition of alphaMSH. Pretreatment of the transfected line with cytokines markedly enhanced stimulation of T-cell proliferation by these tumour cells, and alphaMSH reduced the interaction between melanoma cells and T-cells for two out of three donors. In summary, under experimental conditions where melanoma cell stimulation of T-cells occurred (generally pretreatment of the cells with interferon-gamma gave the most convincing response), alphaMSH reduced this response in the majority of experiments, providing preliminary evidence to confirm the hypothesis that MSH may assist melanoma cells to evade interaction with immune cells.
鉴于我们实验室之前的研究表明，α-黑素细胞刺激素（αMSH）可降低肿瘤坏死因子-α（TNFα）刺激的正常和转化黑素细胞中细胞间黏附分子-1（ICAM-1）的上调，本研究旨在探讨αMSH是否影响黑素瘤细胞与T淋巴细胞的相互作用。最初检测了两种皮肤黑素瘤细胞系——A375-SM和HBL。A375-SM细胞仅使T细胞增殖增加两倍，用细胞因子预处理黑素瘤细胞对此改善不大。HBL细胞诱导T细胞增殖增加三倍，添加细胞因子可使其略有增强。两种细胞系均不表达B7(1)，HBL细胞表达低水平的B7(2)，而A375-SM细胞几乎不表达B7(2)（若有表达也极少）。在某些但并非所有条件下，添加αMSH可减少这些皮肤黑素瘤细胞与T淋巴细胞之间的相互作用。转染了B7的眼黑素瘤细胞系与T细胞有适度的相互作用（在三名供体中有两名出现这种情况），添加αMSH可降低这种反应。用细胞因子预处理转染细胞系可显著增强这些肿瘤细胞对T细胞增殖的刺激，并且对于三名供体中的两名，αMSH减少了黑素瘤细胞与T细胞之间的相互作用。总之，在黑素瘤细胞刺激T细胞的实验条件下（一般用γ干扰素预处理细胞可得到最明显的反应），在大多数实验中αMSH降低了这种反应，为证实MSH可能帮助黑素瘤细胞逃避与免疫细胞相互作用这一假说提供了初步证据。
