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早期子宫内膜癌中肿瘤浸润 T 细胞的预后意义。

Prognostic implications of tumor-infiltrating T cells in early-stage endometrial cancer.

机构信息

Molecular Pathology and Therapeutic Targets Group, Instituto de Investigación Biomédica del Hospital La Paz (IdiPAZ), Madrid, Spain.

Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.

出版信息

Mod Pathol. 2022 Feb;35(2):256-265. doi: 10.1038/s41379-021-00930-7. Epub 2021 Oct 12.

Abstract

Patients with endometrial cancer differ in terms of the extent of T-cell infiltration; however, the association between T-cell subpopulations and patient outcomes remains unexplored. We characterized 285 early-stage endometrial carcinoma samples for T-cell infiltrates in a tissue microarray format using multiplex fluorescent immunohistochemistry. The proportion of T cells and their subpopulations were associated with clinicopathological features and relapse-free survival outcomes. CD3+ CD4+ infiltrates were more abundant in the patients with higher grade or non-endometrioid histology. Cytotoxic T cells (CD25+, PD-1+, and PD-L1+) were strongly associated with longer relapse-free survival. Moreover, CD3+ PD-1+ stromal cells were independent of other immune T-cell populations and clinicopathological factors in predicting relapses. Patients with high stromal T-cell fraction of CD3+ PD-1+ cells were associated with a 5-year relapse-free survival rate of 93.7% compared to 79.0% in patients with low CD3+ PD-1+ fraction. Moreover, in patients classically linked to a favorable outcome (such as endometrioid subtype and low-grade tumors), the stromal CD3+ PD-1+ T-cell fraction remained prognostically significant. This study supports that T-cell infiltrates play a significant prognostic role in early-stage endometrial carcinoma. Specifically, CD3+ PD-1+ stromal cells emerge as a promising novel prognostic biomarker.

摘要

子宫内膜癌患者的 T 细胞浸润程度存在差异;然而,T 细胞亚群与患者预后之间的关系仍未得到探索。我们使用多重荧光免疫组织化学方法,在组织微阵列格式下对 285 例早期子宫内膜癌样本进行 T 细胞浸润分析。T 细胞及其亚群的比例与临床病理特征和无复发生存结局相关。CD3+CD4+浸润在高级别或非子宫内膜样组织学患者中更为丰富。细胞毒性 T 细胞(CD25+、PD-1+和 PD-L1+)与无复发生存时间延长密切相关。此外,CD3+PD-1+基质细胞与其他免疫 T 细胞群体和临床病理因素独立,可预测复发。CD3+PD-1+细胞高基质 T 细胞分数的患者 5 年无复发生存率为 93.7%,而 CD3+PD-1+细胞低基质 T 细胞分数的患者为 79.0%。此外,在与良好预后相关的患者(如子宫内膜样亚型和低级别肿瘤)中,基质 CD3+PD-1+T 细胞分数仍然具有预后意义。这项研究支持 T 细胞浸润在早期子宫内膜癌中发挥重要的预后作用。具体而言,CD3+PD-1+基质细胞是一种很有前途的新型预后生物标志物。

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