Yavorski John M, Blanck George
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Mol Clin Oncol. 2017 Dec;7(6):1119-1121. doi: 10.3892/mco.2017.1432. Epub 2017 Sep 29.
The role of tumor cell expression of major histocompatibility class II (MHCII) has been controversial, with evidence indicating that tumor cell expression of MHCII may lead to an anti-tumor immune response and to tumor cell apoptosis and that MHCII has pro-tumorigenic functions. The cancer genome atlas (TCGA) indicates numerous deleterious mutations for the highly specific, MHCII transcriptional activation proteins, RFX5, RFXAP, RFXANK and CIITA. Also, mutations in the non-polymorphic, human leukocyte antigen (HLA)-DRA gene, which encodes the heavy chain for the most prominent human MHCII molecule, HLA-DR, are common. For many, if not most TCGA cancer datasets, the MHCII specific mutations do not associate with clinical outcomes. However, stomach carcinoma represents an exception, where the data indicate that MHCII-specific mutations are associated with a more favorable outcome. These data raise the question of whether stomach cancer mutations represent effective haploinsufficiency or whether mutations that are associated with a favorable outcome occur with other stomach cancer molecular features that limit the function of the two alleles that represent these MHCII-related proteins.
主要组织相容性复合体II类（MHCII）在肿瘤细胞中的表达作用一直存在争议，有证据表明肿瘤细胞表达MHCII可能引发抗肿瘤免疫反应并导致肿瘤细胞凋亡，同时也表明MHCII具有促肿瘤发生的功能。癌症基因组图谱（TCGA）显示，高度特异性的MHCII转录激活蛋白RFX5、RFXAP、RFXANK和CIITA存在大量有害突变。此外，编码最主要的人类MHCII分子HLA-DR重链的非多态性人类白细胞抗原（HLA）-DRA基因的突变也很常见。对于许多（如果不是大多数）TCGA癌症数据集而言，MHCII特异性突变与临床结果并无关联。然而，胃癌是个例外，数据表明MHCII特异性突变与更有利的结果相关。这些数据引发了一个问题，即胃癌突变是否代表有效的单倍剂量不足，或者与有利结果相关的突变是否与其他限制代表这些MHCII相关蛋白的两个等位基因功能的胃癌分子特征同时出现。
