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颌骨骨肉瘤肿瘤微环境特征分析:迈向预后标志物和新治疗靶点

英文原题:Characterization of the Tumor Microenvironment in Jaw Osteosarcomas, towards Prognostic Markers and New Therapeutic Targets.

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Characterization of the Tumor Microenvironment in Jaw Osteosarcomas, towards Prognostic Markers and New Therapeutic Targets.

PubMed 2023/02/04(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

背景——本研究的目的是探讨颌骨骨肉瘤(JO)的骨吸收以及血管和免疫微环境,并将这些特征与患者的临床结局相关联。方法——我们通过组织微阵列(TMAs)的免疫组化分析研究了50例JO活检样本。

我们检测了骨重塑标志物RANK/RANKL/OPG、内皮糖蛋白CD146,以及免疫环境生物标志物(巨噬细胞的CD163和CD68、TIL(肿瘤浸润淋巴细胞)(TILs)的CD4+和CD8+,以及免疫检查点PD-1/PD-L1)。分析这些生物标志物对进展(复发和转移)、总生存期(OS)和无病生存期(DFS)的影响。结果——发现CD163染色与较低的OS和DFS之间存在强且显著的相关性。CD4+和CD8+染色水平较低,与生存结局的相关性不显著。在肿瘤样本中发现高水平的RANK和RANKL,并与较低的DFS相关。结论——我们的研究结果表明,CD163+ TAMs代表JO预后不良的标志物。靶向TAMs可能是JO中有价值的治疗策略。

展开英文摘要原文

Background-The purpose of this study was to investigate the bone resorption, as well as the vascular and immune microenvironment, of jaw osteosarcomas (JO) and to correlate these features with patient clinical outcomes. Methods-We studied 50 JO biopsy samples by immunohistochemical analysis of tissue microarrays (TMAs).

We investigated the bone remodeling markers RANK/RANKL/OPG, the endothelial glycoprotein CD146, and biomarkers of the immune environment (CD163 and CD68 of macrophages, CD4+ and CD8+ of tumor-infiltrating lymphocytes (TILs), and an immune checkpoint PD-1/PD-L1). The biomarkers were analyzed for their influence on progression (recurrence and metastasis), overall survival (OS), and disease-free survival (DFS).

Results-A strong and significant correlation has been found between CD163 staining and lower OS and DFS. The level of CD4+ and CD8+ staining was low and non-significantly associated with survival outcomes. High levels of RANK and RANKL were found in the tumor samples and correlated with lower DFS. Conclusion-Our findings suggest that CD163+ TAMs represent markers of poor prognosis in JO. Targeting TAMs could represent a valuable therapeutic strategy in JO.

论文信息

作者
Bertin H、Peries S、Amiaud J、Van Acker N、Perrot B、Bouvier C、Aubert S、Marie B
第一作者单位
Department of Maxillofacial Surgery, Nantes University Hospital, 44000 Nantes, France.France
通讯作者单位
Cancer Biobank of Toulouse, IUCT Oncopole, Toulouse University Hospital, 31100 Toulouse, France.France
期刊
Cancers2023 Feb 4
原文标识
PubMed 36831348 · DOI 10.3390/cancers15041004