REDUCTION IN SUSCEPTIBILITY TO NATURAL-KILLER-CELL MEDIATED LYSIS OF HUMAN FO-1 MELANOMA-CELLS AFTER INDUCTION OF HLA CLASS-I ANTIGEN EXPRESSION BY TRANSFECTION WITH B2M GENE
REDUCTION IN SUSCEPTIBILITY TO NATURAL-KILLER-CELL MEDIATED LYSIS OF HUMAN FO-1 MELANOMA-CELLS AFTER INDUCTION OF HLA CLASS-I ANTIGEN EXPRESSION BY TRANSFECTION WITH B2M GENE
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DOI：
10.1172/jci115289
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发表时间：
1991-07-01
影响因子：
15.9
通讯作者：
FERRONE, S
中科院分区：
文献类型：
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作者：
MAIO, M;ALTOMONTE, M;FERRONE, S
在用人或小鼠B2 m基因转染后，在培养的黑色素瘤细胞FO-1上诱导HLA I类抗原与其对自然杀伤（NK）细胞介导的裂解的易感性的统计学显著降低相关。 这些结果表明，人和小鼠β-2-mu之间的结构差异不会消除HLA I类分子复合物调节NK细胞介导的黑素瘤细胞FO-1溶解的能力。 HLA I类抗原在该现象中的作用通过抗HLA I类MAb增强转染的FO-1细胞对NK细胞介导的裂解的易感性的能力得到证实，尽管程度不同。 γ干扰素（IFN-γ）和肿瘤坏死因子-α（TNF-α）显着降低了NK细胞介导的转染FO-1细胞裂解的易感性。 令人惊讶的是，TNF-α比IFN-γ更能降低溶解的程度，尽管后者比前者更能增强HLA I类抗原的表达。 这一发现，结合与IFN-γ或TNF-α孵育的未转染FO-1细胞对NK细胞介导的裂解的敏感性的降低，表明这两种细胞因子不仅通过调节HLA I类抗原的表达，而且通过调节其他结构的表达来减少NK细胞介导的转染细胞的裂解。 诱导HLA I类抗原及其与IFN-γ的调制并不影响淋巴因子激活的杀伤（LAK）细胞介导的转染FO-1细胞裂解的易感性。 表征黑色素瘤细胞HLA I类抗原表达异常的潜在分子机制以及这些分子在黑色素瘤细胞与各种类型效应细胞相互作用中的作用，可能提示新的黑色素瘤免疫治疗方法。
Induction of HLA class I antigens on cultured melanoma cells FO-1 after transfection with a human or a mouse B2m gene was associated with a statistically significant reduction in their susceptibility to natural killer (NK) cell-mediated lysis. These results indicate that the structural differences between human and mouse beta-2-mu do not abolish the ability of the HLA class I molecular complex to modulate NK cell-mediated lysis of melanoma cells FO-1. The role of HLA class I antigens in the phenomenon is corroborated by the ability of anti-HLA class I MAb to enhance, although to a different extent, the susceptibility of transfected FO-1 cells to NK cell-mediated lysis. Gamma interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) significantly reduced the susceptibility to NK cell-mediated lysis of transfected FO-1 cells. Surprisingly, TNF-alpha reduced the extent of lysis more than IFN-gamma, although the latter cytokine enhanced HLA class I antigen expression more than the former one. This finding, in conjunction with a reduction in the susceptibility to NK cell-mediated lysis of untransfected FO-1 cells incubated with IFN-gamma or TNF-alpha, suggests that the two cytokines reduce NK cell-mediated lysis of transfected cells by modulating not only the expression of HLA class I antigens, but also that of other structures. Induction of HLA class I antigens and their modulation with IFN-gamma did not affect the susceptibility to lymphokine-activated killer (LAK) cell-mediated lysis of transfected FO-1 cells. Characterization of the molecular mechanism(s) underlying abnormalities in HLA class I antigen expression by melanoma cells and of the role of these molecules in the interactions of melanoma cells with various types of effector cells may suggest novel immunotherapeutic approaches to melanoma.