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肿瘤相关巨噬细胞在软骨母细胞瘤中的预后意义及其与辅助放疗反应的关系

Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy.

作者信息

Zheng Bo-Wen, Yang Min-Liang, Huang Wei, Zheng Bo-Yv, Zhang Tao-Lan, Li Jing, Lv Guo-Hua, Yan Yi-Guo, Zou Ming-Xiang

机构信息

Department of Spine Surgery, The First Affiliated Hospital, University of South China, Hengyang, 421001, People's Republic of China.

Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, People's Republic of China.

出版信息

J Inflamm Res. 2021 May 17;14:1991-2005. doi: 10.2147/JIR.S308707. eCollection 2021.

Abstract

OBJECTIVE

Chondroblastoma (CB) is a rare and locally growing cartilage-derived tumor. Currently, clinical implications of tumor-associated macrophages (TAMs) in CB remain unclear. In this study, we sought to analyze the relationship between TAM parameters (including densities of CD68+ and CD163+ cells as well as the CD163+/CD68+ ratio) and clinicopathological characteristics and survival of patients.

METHODS

Immunohistochemistry was used to assess TAM subtypes for CD68 and CD163, as well as the expression levels of p53, CD34, and Ki-67 on tumor cells in 132 tissue specimens retrieved between July 2002 and April 2020. Then, TAM parameters were retrospectively analyzed for their associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]) and clinicopathological features.

RESULTS

TAM densities were significantly higher in axial chondroblastoma tissue than in extra-axial chondroblastoma tissue. Moreover, the number of CD163+ TAMs was positively correlated with tumor invasion of surrounding tissues and high expression of CD34 and Ki-67 on tumor cells, whereas CD163+ cell density and the CD163/CD68 ratio were negatively associated with patient response to adjuvant radiotherapy. Univariate Kaplan-Meier analysis revealed that the number of CD68+ and CD163+ lymphocytes was significantly associated with both LRFS and OS. Multivariate Cox regression analysis showed that CD163+ and CD68+ cell levels were independent prognostic factors of LRFS, while TAM data independently predicted OS. More importantly, in subgroup analysis based on three significant factors in univariate survival analysis (including tumor location, adjuvant radiotherapy, and surrounding tissue invasion by tumors), the TAM parameters still displayed good prognostic performance.

CONCLUSION

These data suggest that TAM may significantly affect the biological behavior of CB. We hypothesize that modulating the TAM level or polarization status in the microenvironment may be an effective approach for CB treatment.

摘要

目的

软骨母细胞瘤(CB)是一种罕见的局部生长的软骨源性肿瘤。目前,肿瘤相关巨噬细胞(TAM)在CB中的临床意义尚不清楚。在本研究中,我们试图分析TAM参数(包括CD68+和CD163+细胞密度以及CD163+/CD68+比值)与患者临床病理特征及生存情况之间的关系。

方法

采用免疫组织化学法评估2002年7月至2020年4月间获取的132份组织标本中肿瘤细胞上CD68和CD163的TAM亚型,以及p53、CD34和Ki-67的表达水平。然后,回顾性分析TAM参数与患者预后(无局部复发生存期[LRFS]和总生存期[OS])及临床病理特征的相关性。

结果

轴向软骨母细胞瘤组织中的TAM密度显著高于轴外软骨母细胞瘤组织。此外,CD163+ TAM的数量与肿瘤对周围组织的侵犯以及肿瘤细胞上CD34和Ki-67的高表达呈正相关,而CD163+细胞密度和CD163/CD68比值与患者对辅助放疗的反应呈负相关。单因素Kaplan-Meier分析显示,CD68+和CD163+淋巴细胞的数量与LRFS和OS均显著相关。多因素Cox回归分析表明,CD163+和CD68+细胞水平是LRFS的独立预后因素,而TAM数据可独立预测OS。更重要的是,在基于单因素生存分析中的三个显著因素(包括肿瘤位置、辅助放疗和肿瘤对周围组织的侵犯)进行的亚组分析中,TAM参数仍显示出良好的预后性能。

结论

这些数据表明TAM可能显著影响CB的生物学行为。我们推测,调节微环境中的TAM水平或极化状态可能是治疗CB的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd48/8139723/6b273f96a060/JIR-14-1991-g0001.jpg

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