Grandis J R, Falkner D M, Melhem M F, Gooding W E, Drenning S D, Morel P A
Department of Otolaryngology and Pharmacology, University of Pittsburgh, Pennsylvania 15213, USA.
Clin Cancer Res. 2000 Jul;6(7):2794-802.
The expression of human leukocyte antigen (HLA) class I molecules on the cell surface is necessary for the presentation of peptide antigens to cytotoxic CD8+ T lymphocytes of the immune system. Down-regulation of HLA class I gene expression has been implicated in tumorigenesis, including squamous cell carcinoma of the head and neck (SCCHN). Loss of MHC class I antigens may be one mechanism by which tumor cells escape immune detection. We performed prospective immunostaining of 26 primary SCCHN tumors and samples of normal mucosa harvested several centimeters away from the primary tumor, using a large panel of antibodies directed against allele-specific as well as monomorphic determinants of HLA class I molecules. Loss of expression of HLA class I proteins in the tumor was found in 50% (13 of 26) of primary tumors and was highly correlated with HLA loss in the corresponding normal mucosa (P < 0.0001). Further analysis demonstrated that the loss of HLA class I expression in the tumor was significantly associated with regional lymph node metastases (nodal stage; P = 0.0388), and that the number of HLA class I alleles lost in the normal mucosa was associated with subsequent development of a new primary aerodigestive tract cancer (P = 0.042). A patient with two metachronous cancers available for analysis had no evidence of HLA loss in the first tumor, demonstrated allelic loss in the second cancer, and subsequently died of disease. These results suggest that the loss of expression of HLA class I alleles may have prognostic implications.
细胞表面人类白细胞抗原（HLA）I类分子的表达对于将肽抗原呈递给免疫系统的细胞毒性CD8 + T淋巴细胞是必需的。HLA I类基因表达的下调与肿瘤发生有关，包括头颈部鳞状细胞癌（SCCHN）。MHC I类抗原的缺失可能是肿瘤细胞逃避免疫检测的一种机制。我们使用一大组针对HLA I类分子等位基因特异性以及单态性决定簇的抗体，对26例原发性SCCHN肿瘤和从原发性肿瘤几厘米外采集的正常黏膜样本进行了前瞻性免疫染色。在50%（26例中的13例）的原发性肿瘤中发现肿瘤中HLA I类蛋白表达缺失，并且与相应正常黏膜中的HLA缺失高度相关（P < 0.0001）。进一步分析表明，肿瘤中HLA I类表达的缺失与区域淋巴结转移（淋巴结分期；P = 0.0388）显著相关，并且正常黏膜中丢失的HLA I类等位基因数量与随后发生的新的原发性气消化道癌症相关（P = 0.042）。一名有两个异时性癌症可供分析的患者，在第一个肿瘤中没有HLA缺失的证据，在第二个癌症中出现等位基因缺失，随后死于该疾病。这些结果表明，HLA I类等位基因表达的缺失可能具有预后意义。
