← 返回

综合免疫炎症表型在接受手术治疗的宫颈癌中的预后价值:生存建模和免疫组化验证

英文原题:Prognostic value of an integrated immune-inflammatory phenotype in surgically treated cervical cancer: survival modeling and immunohistochemical validation.

查看英文原题

Prognostic value of an integrated immune-inflammatory phenotype in surgically treated cervical cancer: survival modeling and immunohistochemical validation.

PubMed 2026/06/16(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

研究概要

结合间质 TILs 与 SII 的综合免疫炎症表型与宫颈癌术后复发风险独立相关,并对应不同的组织免疫状态。

中文摘要

宫颈癌术后复发风险存在异质性,传统临床病理因素可能无法充分反映免疫微环境和全身炎症的作用。我们研究了整合间质TIL(肿瘤浸润淋巴细胞)和全身免疫炎症指数(SII)的免疫炎症表型,能否改善术后无复发生存期(RFS)分层。

本回顾性队列研究纳入2020年1月至2025年12月期间接受初次手术的612例宫颈癌患者。在苏木精-伊红切片上评估间质TIL,并依据治疗前血细胞计数计算SII。将整合免疫炎症表型分为有利、不良或中间型。采用Kaplan-Meier分析、限制性立方样条建模及多变量Cox回归。使用C指数、时间依赖AUC、综合Brier评分(IBS)、校准度和36个月里程碑决策曲线分析,比较临床Cox模型、免疫扩展Cox模型、LASSO-Cox、CoxBoost和随机生存森林(RSF)的预后表现。通过免疫组化检测CD8、CD163和PD-L1进行组织层面验证。

随访期间有119例患者发生RFS事件。Kaplan-Meier分析显示,不同TIL类别、SII类别及整合表型之间RFS差异显著。限制性立方样条分析显示,SII与复发风险总体显著相关,且无明显非线性。多变量分析中,FIGO IIIC期、切缘阳性和不良整合表型均与RFS较差独立相关。模型比较显示,免疫扩展Cox模型IBS最低(0.278);LASSO-Cox的C指数最高(0.782),且24和36个月区分能力最佳;RSF的60个月AUC最高。在36个月决策曲线分析中,LASSO-Cox和RSF在中间阈值范围内净获益最高。免疫组化验证显示,有利表型的CD8+细胞密度较高、CD163+细胞密度较低、CD8/CD163比值较高,且PD-L1综合阳性评分较高。

整合间质TIL和SII的免疫炎症表型与宫颈癌术后复发风险独立相关,并对应不同组织免疫状态。该表型可能为复发风险分层提供实用框架,LASSO-Cox和RSF则提供互补的预后评估视角。

展开英文摘要原文

Postoperative recurrence risk in cervical cancer remains heterogeneous, and conventional clinicopathological factors may not fully capture the contribution of the immune microenvironment and systemic inflammation. We investigated whether an integrated immune-inflammatory phenotype combining stromal tumor-infiltrating lymphocytes (TILs) and the systemic immune-inflammation index (SII) could improve recurrence-free survival (RFS) stratification after surgery.

This retrospective cohort study included 612 patients with cervical cancer who underwent primary surgery between January 2020 and December 2025. Stromal TILs were assessed on hematoxylin-eosin sections, and pretreatment SII was calculated from blood counts. An integrated immune-inflammatory phenotype was defined as favorable, poor, or intermediate. Kaplan-Meier analysis, restricted cubic spline modeling, and multivariable Cox regression were performed. Prognostic performance was compared across a clinical Cox model, an immune-extended Cox model, LASSO-Cox, CoxBoost, and random survival forest (RSF) using C-index, time-dependent area under the curve (AUC), integrated Brier score (IBS), calibration, and 36-month landmark decision curve analysis. Tissue-level validation was performed using immunohistochemical assessment of CD8, CD163, and PD-L1.

During follow-up, 119 patients experienced an RFS event. Kaplan-Meier analysis showed significant RFS differences according to TIL category, SII category, and integrated phenotype. Restricted cubic spline analysis demonstrated a significant overall association between SII and recurrence risk, without marked nonlinearity. In multivariable analysis, FIGO IIIC disease, positive margin status, and the poor integrated phenotype remained independently associated with worse RFS. In model comparison, the immune-extended Cox model had the lowest IBS (0.278), LASSO-Cox achieved the highest C-index (0.782) and the best discrimination at 24 and 36 months, and RSF showed the highest 60-month AUC. In 36-month decision curve analysis, LASSO-Cox and RSF showed the greatest net benefit at intermediate thresholds. Immunohistochemical validation showed that the favorable phenotype was characterized by higher CD8+ cell density, lower CD163+ cell density, a higher CD8/CD163 ratio, and higher PD-L1 combined positive score.

An integrated immune-inflammatory phenotype combining stromal TILs and SII was independently associated with postoperative recurrence risk in cervical cancer and corresponded to distinct tissue immune states. This phenotype may provide a practical framework for recurrence risk stratification, while LASSO-Cox and RSF offer complementary prognostic perspectives.

论文信息

作者
Ran L、Lian Z、Tian Y、Qin L、Xiang Y、Yan X、Shui C
单位
Department of Obstetrics and Gynecology, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, China.China
期刊
Frontiers in immunology2026
原文标识
PubMed 42382777 · DOI 10.3389/fimmu.2026.1850891