Department of Gynecologic Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Mod Pathol. 2022 Feb;35(2):266-273. doi: 10.1038/s41379-021-00901-y. Epub 2021 Sep 7.
V-domain Ig-containing suppressor of T-cell activation (VISTA) is a novel immune checkpoint protein and a potential immunotherapeutic target. However, its expression in endometrial cancer has not been clearly defined. This study aimed to investigate VISTA expression and determine its associations with clinicopathological features, molecular subtypes, programmed cell death-ligand 1 (PD-L1) expression, CD8+ T-cell count, and survival in a cohort of 839 patients with endometrial cancer. Using direct sequencing of the polymerase epsilon (POLE) exonuclease domain and immunohistochemistry for mismatch repair (MMR) proteins and p53, we stratified endometrial cancers into four molecular subtypes: POLE ultramutated, MMR-deficient, p53-mutant, and nonspecific molecular profile (NSMP). PD-L1, CD8, and VISTA were detected via immunohistochemistry. VISTA was expressed in the immune cells of 76.6% (643/839) of the samples and in the tumor cells of 6.8% (57/839). VISTA positivity in the immune cells was frequent in tumors staged I-III, those with positive PD-L1 or high CD8+ T-cell density, and those representing POLE ultramutated and MMR-deficient subtypes. Furthermore, VISTA positivity in tumor cells was more frequent in clear cell carcinoma samples. VISTA in immune cells was associated with improved survival in the entire cohort as well as in the endometrioid histology, stage I, PD-L1-negative, MMR-deficient, MMR-proficient, and high and low number of CD8+ T-cell-infiltrated tumor subgroups. VISTA in immune cells was a prognostic factor overall, as well as in patients with endometrioid histology, independent of molecular subtype or CD8+ T-cell density. The data produced by this study, which was the largest to focus on VISTA expression in patients with endometrial cancer to date, suggest that VISTA is a predictor of improved survival.
V-结构域免疫球蛋白抑制 T 细胞激活因子(VISTA)是一种新型免疫检查点蛋白,也是一种有潜力的免疫治疗靶点。然而,其在子宫内膜癌中的表达尚未明确界定。本研究旨在调查 VISTA 的表达,并确定其与临床病理特征、分子亚型、程序性细胞死亡配体 1(PD-L1)表达、CD8+T 细胞计数以及 839 例子宫内膜癌患者生存的相关性。我们通过聚合酶 epsilon(POLE)外切酶结构域的直接测序以及错配修复(MMR)蛋白和 p53 的免疫组化,将子宫内膜癌分为四个分子亚型:POLE 超突变型、MMR 缺陷型、p53 突变型和非特异性分子特征(NSMP)。我们通过免疫组化检测 PD-L1、CD8 和 VISTA。VISTA 在 76.6%(643/839)的样本中的免疫细胞中表达,在 6.8%(57/839)的肿瘤细胞中表达。在 I-III 期肿瘤、PD-L1 阳性或 CD8+T 细胞密度高的肿瘤以及 POLE 超突变型和 MMR 缺陷型肿瘤中,免疫细胞中 VISTA 阳性率较高。此外,在透明细胞癌样本中,肿瘤细胞中 VISTA 阳性率更高。在整个队列中,以及在子宫内膜样组织学、I 期、PD-L1 阴性、MMR 缺陷型、MMR 功能完整型以及 CD8+T 细胞浸润肿瘤亚组中,VISTA 在免疫细胞中的阳性与生存改善相关。在整个队列中,VISTA 在免疫细胞中的阳性是一个预后因素,在子宫内膜样组织学、独立于分子亚型或 CD8+T 细胞密度的患者中也是如此。本研究的数据是迄今为止最大规模的聚焦于子宫内膜癌患者 VISTA 表达的研究,表明 VISTA 是生存改善的预测因子。
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