SELECTIVE CHANGES IN EXPRESSION OF HLA CLASS-I POLYMORPHIC DETERMINANTS IN HUMAN SOLID TUMORS
SELECTIVE CHANGES IN EXPRESSION OF HLA CLASS-I POLYMORPHIC DETERMINANTS IN HUMAN SOLID TUMORS
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DOI：
10.1073/pnas.86.17.6719
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发表时间：
1989-09-01
影响因子：
11.1
通讯作者：
RUSSO, C
中科院分区：
文献类型：
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作者：
NATALI, PG;NICOTRA, MR;RUSSO, C
用单克隆抗体（mab）对主要组织相容性复合体I类抗原的框架决定因素进行手术活检分析表明，恶性转化经常与这些细胞表面分子的显著丧失相关。本研究旨在确定是否会发生主要组织相容性复合体I类表达的更多选择性损失。使用mAb BB7.2对来自13种不同类型的原发性和转移性肿瘤的多个标本进行检测，该抗体可识别多态HLA-A2表位。在每种情况下，HLA- a、B、C分子的表达均通过针对HLA I类框架决定因子的mAb W6/32检测。我们发现，在HLA-A2阳性患者（通过其正常组织与mAb BB7.2的反应性来鉴定）中，HLA-A2产物在70-80%的子宫内膜、结直肠、乳腺和肾脏肿瘤中检测不到或表达降低；40-60%的软组织、皮肤、卵巢、膀胱、前列腺和胃肿瘤；在25-30%的黑色素瘤和肺癌中。所有肿瘤均表达框架HLA-A、B、C决定因子。mAb BB7.2识别的HLA-A2表位位于假定与t细胞受体发生反应的HLA-A2分子的一部分。对肿瘤的免疫监视被认为依赖于细胞毒性T细胞和自然杀伤细胞，前者需要对多态性HLA I类抗原表位进行共同识别，后者则相反，在缺乏HLA I类抗原时被激活。本研究显示的HLA I类多态性表位的选择性缺失可能解释了肿瘤细胞逃避t细胞识别和自然杀伤细胞监视的机制。
Analysis of surgical biopsies with monoclonal antibodies (mAbs) to framework determinants of major histocompatibility complex class I antigens has shown that malignant transformation is frequently associated with a marked loss of these cell surface molecules. The present study sought to determine whether more selective losses of major histocompatibility complex class I expression occur. Multiple specimens from 13 different types of primary and metastatic tumors were tested utilizing mAb BB7.2, which recognizes a polymorphic HLA-A2 epitope. In each case, expression of HLA-A,B,C molecules was determined by testing with mAb W6/32 directed to a framework HLA class I determinant. We have found that in HLA-A2-positive patients (identified by reactivity of their normal tissues with mAb BB7.2), HLA-A2 products are not detectable or are reduced in their expression in 70-80% of endometrial, colorectal, mammary, and renal tumors; in 40-60% of soft-tissue,skin, ovary, urinary bladder, prostate and stomach tumors; and in 25-30% of melanomas and lung carcinomas tested. All tumors expressed the framework HLA-A,B,C determinant. The HLA-A2 epitope recognized by mAb BB7.2 is located in a portion of the HLA-A2 molecule postulated to react with the T-cell receptor. Immune surveillance to tumors is thought to depend on cytotoxic T cells, which require corecognition of polymorphic HLA class I epitopes, and on natural killer cells, which are, on the contrary, activated by the absence of HLA class I antigens. The selective loss of an HLA class I polymorphic epitope shown in this study may explain the mechanism by which tumor cells escape both T-cell recognition and natural killer cell surveillance.