Natali P G, Nicotra M R, Bigotti A, Venturo I, Marcenaro L, Giacomini P, Russo C
Department of Immunology, Regina Elena Cancer Institute, Rome, Italy.
Proc Natl Acad Sci U S A. 1989 Sep;86(17):6719-23. doi: 10.1073/pnas.86.17.6719.
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.
用针对主要组织相容性复合体I类抗原构架决定簇的单克隆抗体（mAb）分析手术活检标本发现，恶性转化常与这些细胞表面分子的显著丢失有关。本研究旨在确定是否发生了主要组织相容性复合体I类表达的更具选择性的丢失。利用识别多态性HLA - A2表位的mAb BB7.2对来自13种不同类型原发性和转移性肿瘤的多个标本进行了检测。在每种情况下，通过用针对构架HLA I类决定簇的mAb W6/32检测来确定HLA - A、B、C分子的表达。我们发现，在HLA - A2阳性患者（通过其正常组织与mAb BB7.2的反应性确定）中，70 - 80%的子宫内膜癌、结直肠癌、乳腺癌和肾癌中检测不到HLA - A2产物或其表达降低；在40 - 60%的软组织、皮肤、卵巢、膀胱癌、前列腺癌和胃癌中；以及在25 - 30%检测的黑色素瘤和肺癌中。所有肿瘤均表达构架HLA - A、B、C决定簇。mAb BB7.2识别的HLA - A2表位位于HLA - A2分子中假定与T细胞受体反应的部分。对肿瘤的免疫监视被认为依赖于细胞毒性T细胞，其需要多态性HLA I类表位的共同识别，以及自然杀伤细胞，相反，自然杀伤细胞因缺乏HLA I类抗原而被激活。本研究中显示的HLA I类多态性表位的选择性丢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。
