CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Characterization of the Tumor Microenvironment in Jaw Osteosarcomas, towards Prognostic Markers and New Therapeutic Targets.
Characterization of the Tumor Microenvironment in Jaw Osteosarcomas, towards Prognostic Markers and New Therapeutic Targets.
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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。
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.
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