最近证明免疫检查点抑制剂对晚期和复发性子宫内膜癌患者有益。这项回顾性研究调查了子宫内膜癌中的免疫检查点分子，因为它们与分子亚型、临床结果和预测价值有关。控制免疫检查点、程序性细胞死亡 1（PD1，由 PDCD1 编码）、其配体（通过定量聚合酶链反应 (qPCR) 测定 239 例子宫内膜癌组织中的 PDL1（由 CD274 编码）和干扰素 γ (IFNG)，并与 25 例对照子宫内膜组织进行比较。使用 ProMiSe 分子分类对总共 81 个子宫内膜癌组织进行了分析，并对整个队列的患者轨迹进行了分析。研究结果在癌症基因组图谱 (TCGA；n=548) 的独立队列中得到验证。与非恶性对照组织相比，子宫内膜癌中的 PD1、PDL1 和 IFNG 表达显着较高，平均表达量为 0.12、0.05、对照组织中分别为 0.44、0.31 和 0.05，子宫内膜癌中分别为 0.44、0.31 和 0.35。 POLE 突变和错配修复缺陷 (MMRd)（免疫热）肿瘤表现出最高的 PD1 和 IFNG 表达。 PD1、PDL1 和 IFNG 表达增加与无复发（分别为 HR 0.32，p<0.001；HR 0.30，p<0.001；HR 0.47，p=0.012）、疾病特异性（HR 0.38，p<分别为 0.001；HR 0.29，p<0.001；HR 0.45，p=0.017），以及总生存率（分别为 HR 0.56，p=0.003；HR 0.38，p<0.001；HR 0.58，p=0.006）。 Cox 回归证实了 PD1 对无复发生存率（HR 0.39，p=0.009）和 PDL1 对总生存率（HR 0.55，p=0.037）的预后意义。肿瘤PD1对无复发生存、疾病特异性生存和总生存的预后价值在TCGA队列中得到证实。控制PD1免疫检查点的肿瘤基因表达，特别是在“热肿瘤”中表达，预测无复发、疾病-两个独立队列中子宫内膜癌患者的特异性和总体生存率。对这些基因的评估可用于对有资格接受免疫检查点抑制剂的患者进行分层，这需要前瞻性临床试验。© IGCS 和 ESGO 2024。CC BY-NC 允许重复使用。禁止商业再利用。由英国医学杂志出版。

Immune checkpoint inhibitors have recently demonstrated benefit in patients with advanced and recurrent endometrial carcinoma. This retrospective study investigated immune checkpoint molecules in endometrial carcinoma as they pertain to the molecular subtypes, clinical outcomes, and predictive value.Tumoral RNA expression of genes controlling the immune checkpoint, programmed cell death 1 (PD1, encoded by PDCD1), its ligand (PDL1, encoded by CD274), and interferon gamma (IFNG) was determined in 239 endometrial carcinoma tissues by quantitative polymerase chain reaction (qPCR) and compared with endometrial tissue from 25 controls. A total of 81 endometrial carcinoma tissues were analyzed using the ProMiSe molecular classification, and patient trajectories were analyzed for the entire cohort. Findings were validated in an independent cohort from The Cancer Genome Atlas (TCGA; n=548).PD1, PDL1, and IFNG expression was significantly higher in endometrial carcinoma when compared with non-malignant control tissue with a mean expression of 0.12, 0.05, and 0.05 in control tissue and 0.44, 0.31, and 0.35 in endometrial carcinoma, respectively. POLE-mutated and mismatch repair-deficient (MMRd) (immunologically hot) tumors showed the highest expression of PD1 and IFNG. Increased expression of PD1, PDL1, and IFNG was associated with improved recurrence-free (HR 0.32, p<0.001; HR 0.30, p<0.001; HR 0.47, p=0.012, respectively), disease-specific (HR 0.38, p<0.001; HR 0.29, p<0.001; HR 0.45, p=0.017, respectively), and overall survival (HR 0.56, p=0.003; HR 0.38, p<0.001; HR 0.58, p=0.006, respectively). Cox regression confirmed the prognostic significance of PD1 for recurrence-free survival (HR 0.39, p=0.009) and PDL1 for overall survival (HR 0.55, p=0.037). The prognostic value of tumoral PD1 on recurrence-free survival, disease-specific survival, and overall survival was confirmed in the TCGA cohort.Tumoral gene expression controlling the PD1 immune checkpoint, particularly expressed in "hot tumors", predicted recurrence-free, disease-specific, and overall survival in patients with endometrial carcinoma in two independent cohorts. Evaluation of these genes could be used to stratify patients who qualify for immune checkpoint inhibitors, which warrants prospective clinical trials.© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.