Heymann D, Godard A, Raher S, Ringeard S, Lassort D, Blanchard F, Harb J
U211 INSERM, Institut de Biologie, Nantes, France.
Cytokine. 1995 Feb;7(2):111-7. doi: 10.1006/cyto.1995.1015.
ICAM-1-mediated cell-cell adhesion is essential for different immunologic functions including non-MHC-restricted cytotoxicity. The shedding of a soluble form of ICAM-1 from melanoma impairs immune recognition and leads to tumour escape. Pretreatment of the Foss human melanoma cell line with HILDA/LIF or OSM, two cytokines involved in acute-phase response, increased the expression of membrane ICAM-1 twofold without inducing sICAM-1 shedding. Conversely, TNF-alpha, in the same conditions, strongly stimulated membrane ICAM-1 expression and the shedding of the soluble form. The same phenomenon was observed on the A375 human melanoma cell line. ICAM-1 upregulation was concomitant with an increase in the non-MHC-restricted cytotoxicity of tumour cells mediated by LAK cell.s This higher sensitivity to LAK lysis was abolished by RR1/1, a specific monoclonal antibody against ICAM-1. Our results demonstrate for the first time the ability of HILDA/LIF and OSM to upregulate ICAM-1 expression on the melanoma cell surface, suggesting a potential role for these cytokines in human immune surveillance during tumour progression.
细胞间黏附分子-1(ICAM-1)介导的细胞间黏附对于包括非主要组织相容性复合体(MHC)限制的细胞毒性在内的不同免疫功能至关重要。黑色素瘤中可溶性ICAM-1的脱落会损害免疫识别并导致肿瘤逃逸。用参与急性期反应的两种细胞因子希尔达/白血病抑制因子(HILDA/LIF)或抑瘤素M(OSM)对福斯人类黑色素瘤细胞系进行预处理,可使膜ICAM-1的表达增加两倍,且不会诱导可溶性ICAM-1(sICAM-1)的脱落。相反,在相同条件下,肿瘤坏死因子-α(TNF-α)强烈刺激膜ICAM-1的表达以及可溶性形式的脱落。在A375人类黑色素瘤细胞系上也观察到了同样的现象。ICAM-1的上调与由淋巴因子激活的杀伤细胞(LAK细胞)介导的肿瘤细胞非MHC限制的细胞毒性增加同时出现。这种对LAK裂解的更高敏感性被RR1/1(一种针对ICAM-1的特异性单克隆抗体)消除。我们的结果首次证明了HILDA/LIF和OSM上调黑色素瘤细胞表面ICAM-1表达的能力,表明这些细胞因子在肿瘤进展过程中的人类免疫监视中可能发挥作用。