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基于 PD-L1 表达和 TIL(肿瘤浸润淋巴细胞)的免疫分型在宫颈腺癌中的预后意义

英文原题:Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinoma.

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Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinoma.

PubMed 2024/12/29(内容时间) Transl Oncol Q2 · IF 4.9(JCR 2025)

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研究概要

NHPVA 人群中的 TMIT I 组最有可能从 PD-L1/PD-1 阻断免疫治疗中获益。ECA 的免疫分型显示出显著的预后价值,提示其可能在指导临床分层和治疗决策方面具有应用潜力。

研究思路结论见上方概要

宫颈管腺癌(ECA)包括一组异质性疾病,近几十年来其发病率显著增加。ECA在组织学上可分为人乳头瘤病毒相关型(HPVA)和非HPVA型(NHPVA)。鉴于各亚型在病理特征和临床行为上的差异,评估它们各自的免疫微环境至关重要。它们可分为不同的肿瘤微环境免疫类型(TMIT)。

共540例手术切除的ECA样本被分为HPVA和NHPVA亚组。采用免疫组化评估肿瘤浸润免疫标志物。我们根据PD-L1和CD8+TIL(肿瘤浸润淋巴细胞)(TILs)表达将ECA分为四种TMIT,并分析其预后意义。

在464例HPVA中观察到319例(68.8%)PD-L1阳性,在76例NHPVA中观察到55例(72.4%)PD-L1阳性。在整个队列中,高CD8+ TILs表达与改善的无病生存期(DFS,p=0.018)和总生存期(OS,p=0.031)显著相关。共有177例样本(32.8%)被归类为TMIT I(高PD-L1和高CD8+ TILs),与其他TMIT组相比,表现出明显更密集的免疫细胞浸润。在NHPVA亚组中,TMIT与DFS(p=0.005)和OS(p=0.003)均显著相关。多因素分析确定TMIT是NHPVA组DFS的独立预后因素,其中TMIT I提示更有利的预后(p=0.042)。

展开英文摘要原文

Endocervical adenocarcinoma (ECA) comprises a heterogeneous group of diseases whose incidence has increased significantly in recent decades. ECA can be histologically classified into human papillomavirus-associated (HPVA) and non-HPVA (NHPVA) types. Given the variability in pathological features and clinical behavior between the subtypes, evaluating their respective immune microenvironments is essential. They can be categorized into distinct tumor microenvironment immune types (TMIT).

A total of 540 surgically resected ECA samples were classified into HPVA and NHPVA subgroups. Tumor-infiltrating immune markers were assessed using immunohistochemistry. We categorized ECA into four TMIT based on PD-L1 and CD8+ tumor-infiltrating lymphocytes (TILs) expression, and analyzed their prognostic significance.

PD-L1 positivity was observed in 319 out of 464 (68.8%) HPVA and 55 out of 76 (72.4%) NHPVA. Across the entire cohort, high CD8+ TILs expression was significantly associated with improved disease-free survival (DFS, p=0.018) and overall survival (OS, p=0.031). A total of 177 samples (32.8%) were classified as TMIT I (high PD-L1 and high CD8+ TILs), exhibiting markedly denser immune cell infiltration compared to the other TMIT groups. In NHPVA subgroup, TMIT was significantly associated with both DFS (p=0.005) and OS (p=0.003). Multivariate analysis identified TMIT as an independent prognostic factor for DFS in the NHPVA group, with TMIT I indicating a more favorable prognosis (p=0.042).

TMIT I group within the NHPVA population is most likely to benefit from PD-L1/PD-1 blockade immunotherapies. The immune classification of ECA demonstrates significant prognostic value, suggesting its potential utility in guiding clinical stratification and therapeutic decision-making.

论文信息

作者
Wei LJ、Wu ZY、Wu LY、Wu YW、Liang HY、Luo RZ、Liu LL
第一作者单位
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.China
通讯作者单位
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address: liulil@sysucc.org.cn.China
期刊
Translational oncology2025 Feb
原文标识
PubMed 39736213 · DOI 10.1016/j.tranon.2024.102265