体外培养中黑色素瘤细胞表面HLAI类分子丢失的鉴定

IdentificationofLossofHLAClassIMoleculesontheSurfaceofMelanomaCellinVitro

应用流式细胞术，从ＨＬＡＡ２阳性人黑色素瘤细胞系（６２４Ｍｅｌ）中选择培养，鉴定出一株丢失ＨＬＡ—Ａ２分子的黑色素瘤细胞（６２４—ｎＭｅｌ），它具有抵抗ＨＬＡＡ２限制的、黑色素瘤抗原肽特异性ＴＩＬ杀伤作用。经ｒＩＦＮγ诱导，能提高６２４－ＭｅｌＨＬＡ－Ａ２分子表达，而不能增强６２４ｎＭｅｌＨＬＡ－Ａ２分子表达和其对ＴＩＬ的敏感性。结果提示，ＴＩＬ对瘤细胞抗原的识别依赖于ＨＬＡⅠ类分子，而瘤细胞ＨＬＡⅠ类分子的缺失可能是肿瘤逃逸机体免疫监视的一个重要因素。

Oneofphenotypesmelanomacellline(624nMel)withdeficiencyinHLAA2moleculeexpressionhasidentifiedfromselectivecultureHLAA2 positivemelanomacelllinebyusingflowcytometry.LossofHLAA2moleculesrenderedmelanomacellsresistanttolysisbyHLAA2restrictedtumorinfiltrationlymphocytes(TIL)whichspecificallyrecognizemelanomaassociatedantigens.Treatmentof624MelwithrIFN resultedinanincreasedexpressionofHLAA2molecules.However,LossofHLAA2moleculeexpressionof624nMelwasnotupregulatedorinduced,andabilityto stimulatingTILandactingastargetoftheseTILwasnotenhancedbyrIFN.TheresultsshowedthattherecognitionofsharedtumorantigenamongmelanomacellswasinaHLAclassIrestrictedmanner,andappeared to be oneofimportantrolesforalteredHLAclassIphenotypesintumorcellsescapemechanismsofhumanimmunosurvillance.