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肿瘤相关巨噬细胞的募集和极化分型与 Wilms 瘤患者的肿瘤进展和预后不良有关。

Recruitment and polarization typing of tumor-associated macrophages is associated with tumor progression and poor prognosis in Wilms tumor patients.

机构信息

Department of Urology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

Chongqing Key Laboratory of Pediatrics, Chongqing, China.

出版信息

PLoS One. 2024 Nov 12;19(11):e0309910. doi: 10.1371/journal.pone.0309910. eCollection 2024.

Abstract

PURPOSE

Tumor-associated macrophages (TAMs) play a crucial role in shaping various tumor microenvironments. However, their recruitment in Wilms tumor (WT), the predominant malignant renal tumor in children, has been inadequately explored. This retrospective cohort study involved the analysis of 148 WT samples to investigate the recruitment and polarization typing of TAMs in WT tissues.

METHODS

WT tissues underwent Western blotting (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence (IF) to measure the expression of TAM markers CD68, CD86, and CD163. Statistically analyze the relationship between TAM recruitment levels and patient clinical characteristics, and use Kaplan-Meier curves and the log-rank test to evaluate the association between TAM levels and survival outcomes.

RESULTS

The findings indicated a positive correlation between the recruitment levels of total macrophages (Mtotal) and M2 tumor-associated macrophages (M2 TAM) in both chemotherapy and non-chemotherapy groups with the clinical stage. Elevated recruitment of Mtotal and M2 TAM in tumor tissues was linked to a poorer prognosis. Notably, patients with persistently higher recruitment of M2 TAM following preoperative chemotherapy exhibited the worst prognosis.

CONCLUSIONS

The recruitment and polarization typing of TAM exhibit significant differences in WT patients with various stages and prognosis outcomes, suggesting a potential avenue for future diagnosis and treatment of WT.

摘要

目的

肿瘤相关巨噬细胞(TAMs)在塑造各种肿瘤微环境中起着至关重要的作用。然而,它们在儿童中主要的恶性肾肿瘤——Wilms 瘤(WT)中的募集作用尚未得到充分探索。本回顾性队列研究分析了 148 例 WT 样本,以研究 WT 组织中 TAMs 的募集和极化分型。

方法

对 WT 组织进行 Western blot(WB)、逆转录定量聚合酶链反应(RT-qPCR)和免疫荧光(IF),以测量 TAM 标志物 CD68、CD86 和 CD163 的表达。统计分析 TAM 募集水平与患者临床特征之间的关系,并使用 Kaplan-Meier 曲线和对数秩检验评估 TAM 水平与生存结果之间的关系。

结果

研究结果表明,在化疗和非化疗组中,总巨噬细胞(Mtotal)和 M2 肿瘤相关巨噬细胞(M2 TAM)的募集水平与临床分期呈正相关。肿瘤组织中 Mtotal 和 M2 TAM 的募集增加与预后不良相关。值得注意的是,术前化疗后持续高募集 M2 TAM 的患者预后最差。

结论

TAM 的募集和极化分型在不同分期和预后结局的 WT 患者中存在显著差异,提示 TAM 可能成为 WT 未来诊断和治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/11556688/1bc15fa10cd8/pone.0309910.g001.jpg

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