Bertin Hélios, Peries Sophie, Amiaud Jérôme, Van Acker Nathalie, Perrot Bastien, Bouvier Corinne, Aubert Sébastien, Marie Béatrice, Larousserie Frédérique, De Pinieux Gonzague, Crenn Vincent, Rédini Françoise, Gomez-Brouchet Anne
Department of Maxillofacial Surgery, Nantes University Hospital, 44000 Nantes, France.
CRCI2NA-Nantes-Angers Cancer and Immunology Research Center, 44000 Nantes, France.
Cancers (Basel). 2023 Feb 4;15(4):1004. doi: 10.3390/cancers15041004.
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.
背景——本研究的目的是调查颌骨骨肉瘤（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果相关联。方法——我们通过组织微阵列（TMA）的免疫组织化学分析研究了50份JO活检样本。我们研究了骨重塑标志物RANK/RANKL/OPG、内皮糖蛋白CD146以及免疫环境的生物标志物（巨噬细胞的CD163和CD68、肿瘤浸润淋巴细胞（TIL）的CD4+和CD8+以及免疫检查点PD-1/PD-L1）。分析了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——已发现CD163染色与较低的OS和DFS之间存在强烈且显著的相关性。CD4+和CD8+染色水平较低，与生存结果无显著关联。在肿瘤样本中发现高水平的RANK和RANKL，且与较低的DFS相关。结论——我们的研究结果表明，CD163+肿瘤相关巨噬细胞代表JO预后不良的标志物。靶向肿瘤相关巨噬细胞可能是JO中一种有价值的治疗策略。
