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MPC-03 IMMUNOHISTOCHEMICAL ANALYSIS OF TUMOR ASSOCIATED MACROPHAGE INDUCED AFTER BIODEGRADABLE CARMUSTINE WAFER IMPLANTATION IN HUMAN GLIOBLASTOMA

机译:MPC-03植入人胶质母细胞瘤后植入肿瘤相关巨噬细胞的免疫组织化学分析

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摘要

The carmustine (BCNU) wafer, a biodegradable polymer, currently is the only drug that is able to be placed at the surgical site to treat malignant tumors. Biomaterials to treat cancers hold therapeutic potential; however, how they behave inside the tumor microenvironment requires further study. We previously investigated the tumor microenvironment after BCNU wafer implantation, and found that CD68-positive macrophage was significantly introduced around the wafer (Shibahara et al. J Neurooncol 2018). Recent studies demonstrated the importance of tumor-associated macrophage (TAM). However, we could not clarify whether the increased macrophage around the wafer was pro-tumor or anti-tumor phenotype. In the present study, we immunohistochemically examined expressions of CD68, IBA1, CD163, TMEM119, BIN1, CD31, and VEGF to investigate TAM after the wafer implantation. Quantitative evaluation revealed that CD68-positive cells were significantly increased (P = 0.0009), whereas TMEM119-positive cells were significantly decreased (P = 0.0081) after wafer implantation compared to tissue from cases without wafer implantation. CD163, a known marker of poor prognosis in glioblastoma, did not differ with and without wafer implantation. Among factor analyzed, BCNU wafer did not induce protumor TAM, but reduced microglial marker, TMEM119. In addition to the aspect of chemotherapy, BCNU wafer may have potential to modify the tumor microenvironment such as TAM.
机译:卡莫司汀(BCNU)晶片是一种可生物降解的聚合物,目前是唯一能够放置在手术部位以治疗恶性肿瘤的药物。治疗癌症的生物材料具有治疗潜力;但是,它们在肿瘤微环境中的行为需要进一步研究。先前我们研究了BCNU晶片植入后的肿瘤微环境,发现CD68阳性巨噬细胞明显引入了晶片周围(Shibahara等人,J Neurooncol 2018)。最近的研究证明了肿瘤相关巨噬细胞(TAM)的重要性。但是,我们无法澄清晶圆周围增加的巨噬细胞是肿瘤前表型还是抗肿瘤表型。在本研究中,我们免疫组织化学检查了CD68,IBA1,CD163,TMEM119,BIN1,CD31和VEGF的表达,以研究晶圆植入后的TAM。定量评估显示,与未植入晶片的组织相比,晶片植入后CD68阳性细胞显着增加(P = 0.0009),而TMEM119阳性细胞显着减少(P = 0.0081)。 CD163是胶质母细胞瘤预后不良的已知标志,在植入和未植入晶片的情况下均无差异。在分析的因素中,BCNU晶片不诱导肿瘤TAM,但减少了小胶质标记物TMEM119。除化学疗法外,BCNU晶片可能具有修饰肿瘤微环境(如TAM)的潜力。

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