Wei Li-Jun, Wu Zi-Yun, Wu Li-Yan, Wu Ying-Wen, Liang Hao-Yu, Luo Rong-Zhen, Liu Li-Li
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.
Department of Urology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China.
Transl Oncol. 2025 Feb;52:102265. doi: 10.1016/j.tranon.2024.102265. Epub 2024 Dec 29.
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.
宫颈管腺癌（ECA）是一组异质性疾病，近几十年来其发病率显著上升。ECA在组织学上可分为人乳头瘤病毒相关（HPVA）和非HPVA（NHPVA）类型。鉴于各亚型之间病理特征和临床行为的差异，评估它们各自的免疫微环境至关重要。它们可被分类为不同的肿瘤微环境免疫类型（TMIT）。
总共540例手术切除的ECA样本被分为HPVA和NHPVA亚组。使用免疫组织化学评估肿瘤浸润免疫标志物。我们根据程序性死亡受体配体1（PD-L1）和CD8 +肿瘤浸润淋巴细胞（TILs）的表达将ECA分为四种TMIT，并分析它们的预后意义。
在464例HPVA中的319例（68.8%）和76例NHPVA中的55例（72.4%）中观察到PD-L1阳性。在整个队列中，高CD8 + TILs表达与无病生存期（DFS，p = 0.018）和总生存期（OS，p = 0.031）的改善显著相关。总共177个样本（32.8%）被分类为TMIT I（高PD-L1和高CD8 + TILs），与其他TMIT组相比，其免疫细胞浸润明显更密集。在NHPVA亚组中，TMIT与DFS（p = 0.005）和OS（p = 0.003）均显著相关。多变量分析确定TMIT是NHPVA组DFS的独立预后因素，TMIT I表明预后更有利（p = 0.042）。
NHPVA人群中的TMIT I组最有可能从PD-L1/程序性死亡受体1（PD-1）阻断免疫疗法中获益。ECA的免疫分类显示出显著的预后价值，表明其在指导临床分层和治疗决策方面的潜在效用。
