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免疫微环境 CD8⁺ TIL(肿瘤浸润淋巴细胞)与 PD-L1 表达在浸润性宫颈鳞状细胞癌中作为预后标志物的相互作用

英文原题:Interplay Between Immune Microenvironment CD8(+) Tumor-Infiltrating Lymphocytes and PDL-1 Expression as Prognostic Markers in Invasive Cervical Squamous Cell Carcinoma.

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Interplay Between Immune Microenvironment CD8(+) Tumor-Infiltrating Lymphocytes and PDL-1 Expression as Prognostic Markers in Invasive Cervical Squamous Cell Carcinoma.

PubMed 2025/11/10(内容时间) Medicina (Kaunas) Q1 · IF 2.9(JCR 2025)

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中文摘要

宫颈癌仍然是全球癌症相关发病率和死亡率的主要原因,晚期疾病的治疗选择有限。随着我们更好地理解肿瘤细胞与肿瘤微环境相互作用的精细机制,新的路径和机会将会出现。近期证据强调了免疫检查点标志物和TIL(肿瘤浸润淋巴细胞)(TILs),尤其是 CD8 + TILs,在影响治疗结局方面的预后和预测作用。

本研究调查了 48 例新诊断、未接受治疗的宫颈癌病例中 PD-L1 和 CD8 + TILs 的免疫组化表达,并分析了它们与临床病理特征和生存结局的关联。

在我们的队列中,我们观察到 PD-L1 阳性见于 68.8% 的病例,最常见于晚期 FIGO 分期以及伴有淋巴血管侵犯或通过 Ki-67 指数评估的高增殖率的肿瘤中。52.1% 的病例观察到高水平的瘤内 CD8 + TILs,并与间质 TILs 呈正相关,与较低的增殖率和无血管侵犯相关。PD-L1 表达与 CD8 + TILs 密度之间发现显著负相关(p = 0.047)。生存分析显示,表现出 CD8 + TILs 低水平和 PD-L1 阳性肿瘤的“冷”免疫表型患者结局更差,而高水平的 CD8 + TILs 起保护作用。

我们的研究强调了 PD-L1 和 CD8 + TILs 生物标志物免疫组化评估的重要性,它们具有互补的相互关系,并对宫颈鳞状细胞癌具有显著的预后影响。PD-L1阳性标志着侵袭性疾病特征,而较高的瘤内CD8 + TIL密度具有保护作用。二者的联合评估可能改善患者分层并为免疫治疗策略提供依据。

展开英文摘要原文

Background : Cervical cancer remains a major cause of cancer-related morbidity and mortality worldwide, with limited therapeutic options for advanced disease. As we better understand the fine mechanisms involved in the interaction between tumor cells and the tumor microenvironment, new paths and opportunities will emerge. Recent evidence highlights the prognostic and predictive roles of immune checkpoint markers and tumor-infiltrating lymphocytes (TILs), especially CD8 + TILs, in shaping treatment outcomes. Objectives : This study investigated the immunohistochemical expression of PD-L1 and CD8 + TILs in 48 newly diagnosed, treatment-naive cervical cancer cases and analyzed their associations with clinicopathological features and survival outcomes. Results : In our cohort, we observed that PD-L1 positivity was identified in 68. 8% of cases, most frequently in advanced FIGO stages and in tumors with lympho-vascular invasion or with a high proliferation rate evaluated by the Ki-67 index.

High levels of intra-tumoral CD8 + TILs were observed in 52. 1% of cases and correlated positively with stromal TILs, lower proliferation rates, and absence of vascular invasion. A significant inverse relationship was found between PD-L1 expression and the density of CD8 + TILs ( p = 0. 047). Survival analysis showed that patients exhibiting a "cold" immunophenotype with low levels of CD8 + TILs and PD-L1-positive tumors had worse outcomes, while high levels of CD8 + TILs played a protective role.

Conclusions : Our study highlights the importance of the immunohistochemical assessment of PD-L1 and CD8 + TILs biomarkers, which have a complementary inter-relationship and have a significant prognostic impact on cervical squamous cell carcinoma. PD-L1 positivity marks aggressive disease features, while higher intra-tumoral CD8 + TIL density is protective. Their combined evaluation may improve patient stratification and inform immunotherapy strategies.

论文信息

作者
Petrică LA、Deacu M、Cozaru GC、Mitroi AF、Bălţătescu GI、Enciu M、Cojocaru O、Nicolau AA
单位
"St. Apostol Andrew" Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania.Italy
期刊
Medicina (Kaunas, Lithuania)2025 Nov 10
原文标识
PubMed 41303843 · DOI 10.3390/medicina61112007