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弥漫大 B 细胞淋巴瘤中肿瘤微环境及 PD-L1 表达与临床病理特征和预后相关性的综合分析

英文原题:Comprehensive Analysis of Tumor Microenvironment and PD-L1 Expression Associations with Clinicopathological Features and Prognosis in Diffuse Large B-Cell Lymphoma.

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Comprehensive Analysis of Tumor Microenvironment and PD-L1 Expression Associations with Clinicopathological Features and Prognosis in Diffuse Large B-Cell Lymphoma.

PubMed 2025/09/06(内容时间) Blood Lymphat Cancer Q2 · IF 3.2(JCR 2025)

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研究概要

TME 在 DLBCL 的生物学行为中起着关键作用,尤其是因为 TIL-T 和 TAMs 与患者生存结局显著相关。

中文摘要

本回顾性研究评估89例原发性DLBCL病例,结合临床病理资料,通过自动化免疫组织化学定量分析肿瘤热点区和微环境区CD3、CD8、FOXP3、CD163及PD-L1表达。采用Kaplan-Meier法和Cox回归分析TIL-T、TAM、PD-L1表达与无进展生存期(PFS)和总生存期(OS)的预后相关性。

CD3+细胞浸润高与Ki-67表达低相关;FOXP3+细胞水平升高与美国东部肿瘤协作组体能状态(ECOG)改善相关。CD163+ TAM水平因NCCN-IPI风险、ECOG和细胞起源而异。肿瘤细胞PD-L1(nPD-L1)阳性与NCCN-IPI评分较高、CD3+ T细胞浸润和CD163+ TAM富集相关。微环境PD-L1(mPD-L1)与年龄、ECOG、B症状及所有T细胞亚群和TAM浸润相关。生存分析显示,CD3+、CD8+和FOXP3+ TIL-T水平较高、CD163+ TAM较多或mPD-L1阳性均与OS延长相关;CD3+浸润和mPD-L1阳性与PFS改善相关。单变量分析发现,B症状、结外受累和TIL-T水平低是OS风险因素,而ECOG 0和mPD-L1阳性具有保护作用。多变量模型证实B症状、结外病变和CD3+ TIL-T是OS独立预测因素;CD3+ TIL-T和B症状独立影响PFS。 讨论:TME对DLBCL生物学行为至关重要,尤其是TIL-T和TAM与患者生存结局显著相关。这些细胞可作为关键生物标志物,并为DLBCL提供新的免疫治疗靶点。

展开英文摘要原文

This retrospective study evaluated 89 primary DLBCL cases, integrating clinicopathological data with automated immunohistochemical quantification of CD3, CD8, FOXP3, CD163, and PD-L1 expression in tumor hotspots and microenvironmental compartments. Prognostic associations of TIL-T, TAMs, and PD-L1 expression with PFS and OS were analyzed via Kaplan-Meier methods and Cox regression.

High CD3+ infiltration correlated with lower Ki-67 expression, while elevated FOXP3+ levels linked to improved Eastern Cooperative Oncology Group Performance Status (ECOG). CD163+ TAMs varied by NCCN-IPI risk, ECOG, and cell of origin. Neoplastic PD-L1 (nPD-L1) positivity associated with higher NCCN-IPI scores, CD3+ T-cell infiltration, and CD163+ TAM enrichment. Microenvironmental PD-L1 (mPD-L1) correlated with age, ECOG, B symptoms, and infiltration of all T-cell subsets and TAMs. Survival analysis revealed prolonged overall survival (OS) with high CD3+, CD8+, FOXP3+ TIL-T, CD163+ TAMs, or mPD-L1 positivity, while progression-free survival (PFS) improved with CD3+ infiltration and mPD-L1. Univariate analysis identified B symptoms, extranodal involvement, and low TIL-T levels as OS risks, whereas ECOG 0 and mPD-L1+ were protective. Multivariate modeling confirmed B symptoms, extranodal disease, and CD3+ TIL-T as independent OS predictors; CD3+ TIL-T and B symptoms independently impacted PFS. DISCUSSION: The TME plays a crucial role in the biological behavior of DLBCL, particularly because TIL-T and TAMs are significantly associated with patient survival outcomes. These cell types may serve as critical biomarkers and provide novel immunotherapy targets in DLBCL.

论文信息

作者
Xie YL、Ke LF、Zhang WW、Kang F、Lu SY、Wu CY、Zhu HH、Wang JC
单位
Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, People's Republic of China.China
期刊
Blood and lymphatic cancer : targets and therapy2025
原文标识
PubMed 40951454 · DOI 10.2147/BLCTT.S545717