Prolonged upregulation of the expression of HLA class I antigens and costimulatory molecules on melanoma cells treated with 5-aza-2′-deoxycytidine (5-AZA-CdR)
Prolonged upregulation of the expression of HLA class I antigens and costimulatory molecules on melanoma cells treated with 5-aza-2′-deoxycytidine (5-AZA-CdR)
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DOI：
10.1097/00002371-199901000-00003
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发表时间：
1999-01-01
影响因子：
3.9
通讯作者：
Maio, M
中科院分区：
文献类型：
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作者：
Coral, S;Sigalotti, L;Maio, M
黑色素瘤细胞的免疫原性及其被宿主细胞毒细胞识别的能力取决于肿瘤细胞上人类白细胞抗原(NLA)I类抗原、共刺激分子和黑色素瘤相关抗原(MAA)的存在和表达水平。在这项研究中，我们证明了DNA去甲基化试剂5-氮杂-2‘-脱氧胞苷(5-aza-2’-deoxcytidine，5-aza-cdr)显著增强了12个黑色素瘤细胞的HLAI类抗原、HLAA1和HLAA2等位基因以及共刺激分子细胞间黏附分子-1和淋巴细胞功能相关抗原-3的结构性表达。这种上调在第4天达到峰值，此后缓慢下降，并在治疗结束32天后恢复到基线水平。此外，5-AZA-CDR治疗诱导了MEL275黑色素瘤细胞中MAGE-1的持续表达；通过逆转录聚合酶链式反应，在治疗结束60天后仍可检测到这一点。相反，5-AZA-CDR不影响所研究的黑色素瘤细胞的高分子量MAA的组成性表达。这些观察，再加上比较5-AZA-CDR和干扰素-γ的效果的数据，强烈表明5-AZA-CDR可能在人类黑色素瘤的主动和/或被动特异性免疫治疗中具有潜在的治疗意义。
The immunogenic potential of melanoma cells and their recognition by the host's cytotoxic cells depends on the presence and on the level of expression of human leukocyte antigen (NLA) class I antigens, costimulatory molecules and melanoma-associated antigens (MAA), on neoplastic cells. In this study, we demonstrate that the DNA hypomethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR), Significantly (p < 0.05) enhanced the constitutive expression of HLA class I antigens, HLA-A1 and -A2 alleles, and of the costimulatory molecules intercellular adhesion molecule-1 and lymphocyte function-associated antigen-3, on a panel of 12 melanoma cells. This upregulation peaked at day 4, slowly decreased thereafter, and returned to baseline levels 32 days after the end of treatment. In addition, treatment with 5-AZA-CdR induced a persistent expression of MAGE-1 in Mel 275 melanoma cells; this was still detectable, by reverse transcriptase polymerase chain reaction, 60 days after the end of treatment. In contrast, 5-AZA-CdR did not affect the constitutive expression of the high molecular weight-MAA by the melanoma cells investigated. These observations, together with data obtained comparing the effect of 5-AZA-CdR with that of interferon-gamma, strongly suggest that 5-AZA-CdR may have prospective therapeutic implications in active and/or passive specific immunotherapy for human melanoma.