Hattori Satomi, Yoshikawa Nobuhisa, Liu Wenting, Matsukawa Tetsuya, Kubokawa Mei, Yoshida Kosuke, Yoshihara Masato, Tamauchi Satoshi, Ikeda Yoshiki, Yokoi Akira, Shimizu Yusuke, Niimi Kaoru, Kajiyama Hiroaki
Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8560, Japan.
Department of Obstetrics and Gynecology Collaborative Research, Bell Research Center, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cancer Immunol Immunother. 2025 Jan 3;74(2):70. doi: 10.1007/s00262-024-03919-8.
We focused on how the immunophenotypes based on the distribution of CD8-positive tumor-infiltrating lymphocytes (TILs) relate to the endometrial cancer (EC) molecular subtypes and patients' prognosis.
Two cohorts of EC patients (total n = 145) were analyzed and categorized using the Molecular Risk Classifier for Endometrial cancer (ProMisE): POLEmut (POLE mutation), MMRd (mismatch repair deficiency), NSMP (no specific molecular profile), and p53abn (p53 abnormality). CD8-positive TILs, within the central tumor and the invasive margin, were examined by using immunohistochemical staining and advanced image-analysis software. It was investigated whether these immunophenotypes correlate with the molecular subtypes and patients' survival. RNA-sequencing (RNA-seq) was used to explore tumor-derived factors influencing these immunophenotypes.
Three distinct immunophenotypes (inflamed, excluded, and desert) based on the CD8-positive TIL patterns were identified in EC patients. Notably, the inflamed phenotype was most frequently observed in the POLEmut and MMRd subtypes, while the desert phenotype was predominant in the NSMP subtype; however, other immunophenotypes were also observed. All p53abn subtype showed the non-inflamed (excluded or desert) phenotype. The prognosis was markedly poorer in the patients with the non-inflamed phenotype than in those with the inflamed phenotype. The RNA-seq analysis showed that the expression of MYC target genes and type-1 interferon response genes was enriched in the non-inflamed phenotype in MMRd and NSMP subtypes, respectively.
Evaluating not only the molecular classification but also the immunophenotype may lead to more personalized immunotherapy in EC and elucidating the mechanisms that underlie the formation of the three immunophenotypes could lead to the discovery of new immunotherapy targets.
我们重点研究基于CD8阳性肿瘤浸润淋巴细胞（TILs）分布的免疫表型如何与子宫内膜癌（EC）分子亚型及患者预后相关。
对两组EC患者（共145例）进行分析，并使用子宫内膜癌分子风险分类器（ProMisE）进行分类：POLEmut（POLE突变）、MMRd（错配修复缺陷）、NSMP（无特定分子特征）和p53abn（p53异常）。通过免疫组化染色和先进的图像分析软件检查肿瘤中心和浸润边缘的CD8阳性TILs。研究这些免疫表型是否与分子亚型及患者生存相关。使用RNA测序（RNA-seq）探索影响这些免疫表型的肿瘤衍生因子。
在EC患者中识别出基于CD8阳性TIL模式的三种不同免疫表型（炎症型、排除型和荒漠型）。值得注意的是，炎症型表型在POLEmut和MMRd亚型中最常观察到，而荒漠型表型在NSMP亚型中占主导；然而，也观察到其他免疫表型。所有p53abn亚型均表现为非炎症型（排除型或荒漠型）表型。非炎症型表型患者的预后明显比炎症型表型患者差。RNA-seq分析表明，MYC靶基因和1型干扰素反应基因的表达分别在MMRd和NSMP亚型的非炎症型表型中富集。
不仅评估分子分类，还评估免疫表型可能会在EC中带来更个性化的免疫治疗，阐明三种免疫表型形成的潜在机制可能会发现新的免疫治疗靶点。
Zotero 插件
