Current immunotherapies are effective only in a subset of patients, likely due to several factors including defects in tumor cell antigen presentation, decreased response to immune effectors, and molecular heterogeneity of cancers. Recent molecular classifications enable the categorization of many tumor types. However, deregulation of major histocompatibility complex (MHC) gene expression is poorly characterized in the context of molecular cancer subtypes. To suppress the confounding effect of immune infiltrates on expression patterns of immunoregulators, we identified and removed genes with strong correlation to estimated immune compartment levels in each tumor type. Next, we reanalyzed a total of 13 TCGA cancer types encompassing 5651 tumors and 485 normal adjacent tissues by performing unsupervised clustering of 14 MHC genes. Subsequently, resultant clusters were statistically compared in terms of expression of other immune-related genes. Three MHC expression clusters were discovered by unsupervised clustering. We identified concordantly decreased expression of MHC genes (MHC-low) in 26 out of 55 molecular subtypes. Consequently, our study underlines the urgent need for designing strategies to enhance tumor MHC expression that could improve immune cold tumor rejection by cytotoxic T lymphocytes.

中文翻译：

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主要组织相容性复合体基因作为免疫性冷分子癌症亚型的治疗机会

当前的免疫疗法仅对一部分患者有效，这可能是由于多种因素造成的，包括肿瘤细胞抗原呈递缺陷、对免疫效应物的反应降低以及癌症的分子异质性。最近的分子分类使许多肿瘤类型的分类成为可能。然而，在分子癌症亚型的背景下，主要组织相容性复合体 (MHC) 基因表达的失调特征很差。为了抑制免疫浸润对免疫调节剂表达模式的混杂影响，我们鉴定并去除了与每种肿瘤类型中估计的免疫区室水平强相关的基因。接下来，我们通过对 14 个 MHC 基因进行无监督聚类，重新分析了总共 13 种 TCGA 癌症类型，包括 5651 个肿瘤和 485 个正常邻近组织。随后，在其他免疫相关基因的表达方面对所得簇进行统计比较。通过无监督聚类发现了三个 MHC 表达簇。我们在 55 种分子亚型中的 26 种中发现 MHC 基因（MHC 低）的表达一致降低。因此，我们的研究强调迫切需要设计增强肿瘤 MHC 表达的策略，以改善细胞毒性 T 淋巴细胞对免疫冷肿瘤的排斥。