内膜癌（EC）中肿瘤浸润淋巴细胞（TIL）数量的增加与生存率的提高有关，但尚不清楚这种预后意义与潜在的EC分子亚型有什么关系。在这项探索性假设生成的研究中，我们试图确定与EC分子亚型（即POLE突变型、微卫星不稳定（MSI高）型、拷贝数（CN）低型和CN高型）相关的免疫特征，并确定它们与患者预后的相关性。我们从癌症基因组图谱获得了232个原发性EC的RNA测序和分子亚型数据。使用单样本基因集富集分析（ssGSEA）和基于估计已知RNA转录本的相对子集的细胞类型鉴定（CIBERSORT）进行大量基因表达数据分离。通过分子亚型确定所产生的免疫特征与总体生存率的相关性。通过ssGSEA和CIBERSORT分别在16/30和6/23个免疫基因集中鉴定出显着差异的富集。通过ssGSEA，在CN高分子亚型的EC中，CD8+细胞的签名与总体生存率的改善相关（p = 0.0108），而在MSI高（p = 0.74）或CN低EC分子亚型中，CD8标志似乎不具有预测性（p = 0.793）。在所有分子亚型中，CN高的EC显示出最低水平的CD8+ T细胞浸润。与抗原诱导的T细胞活化和衰竭一致，免疫调节受体的富集主要出现在MSI高和POLE突变型的EC中。大量基因表达数据的分离可以用于确定免疫浸润的子群，进而改善内膜癌的生存率。这些数据支持疾病分子亚群中存在独特的免疫抵抗机制。版权所有© 2023 Elsevier Inc.。保留所有权利。

Increased numbers of tumor infiltrating lymphocytes (TIL) in endometrial cancer (EC) are associated with improved survival, but it is unclear how this prognostic significance relates to the underlying EC molecular subtype. In this explorative hypothesis-generating study, we sought to define the immune signatures associated with the molecular subtypes of EC (i.e., POLE-mutated, microsatellite unstable (MSI-high), copy number (CN)-low, and CN-high) and to determine their correlation with patient outcomes.RNA-sequencing and molecular subtype data of 232 primary ECs were obtained from The Cancer Genome Atlas. Deconvolution of bulk gene expression data was performed using single sample Gene Set Enrichment Analysis (ssGSEA) and Cell type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT). The association of the resultant immune signatures with overall survival was determined across molecular subtypes.Statistically significant differences in enrichment were identified in 16/30 and 6/23 immune gene sets by ssGSEA and CIBERSORT, respectively. Signature of CD8+ cells in ECs of CN-high molecular subtype was associated with improved overall survival by ssGSEA (p = 0.0108), while CD8 signatures did not appear to be prognostic in MSI-high (p = 0.74) or CN-low EC molecular subtypes (p = 0.793). Of all molecular subtypes, CN-high ECs exhibited the lowest levels of CD8+ T cell infiltration. Consistent with antigen-induced T cell activation and exhaustion, enrichment for immunomodulatory receptors was predominantly observed in ECs of MSI-high and POLE-mutated molecular subtypes.Deconvolution of bulk gene expression data can be used to identify populations of immune infiltrated endometrial cancers with improved survival. These data support the existence of unique mechanisms of immune resistance within molecular subgroups of the disease.Copyright © 2023 Elsevier Inc. All rights reserved.