Expression and Regulation of B7-H3 Immunoregulatory Receptor, in Human Mesothelial and Mesothelioma Cells: Immunotherapeutic Implications
Expression and Regulation of B7-H3 Immunoregulatory Receptor, in Human Mesothelial and Mesothelioma Cells: Immunotherapeutic Implications
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DOI：
10.1002/jcp.22600
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发表时间：
2011-10-01
影响因子：
5.6
通讯作者：
Maio, Michele
中科院分区：
文献类型：
--
作者：
Calabro, Luana;Sigalotti, Luca;Maio, Michele
没有治疗可以延长恶性间皮瘤（MM）患者的生存期。由于 MM 会引发抗肿瘤宿主的免疫反应，因此免疫疗法是一种有前景的控制策略。针对调节 T 细胞活化的 B7 免疫调节分子家族成分的免疫调节抗体正在人类恶性肿瘤（包括多发性骨髓瘤）中进行研究。通过流式细胞术和分子分析，在人间皮细胞 (HMC) 的原代培养物和 MM 细胞系中，以及通过免疫组织化学在 MM 组织中研究了 B7 家族的新成分 B7-H3 的表达。还研究了 DNA 低甲基化剂在调节 MM 细胞中 B7-H3 表达水平中的作用。逆转录聚合酶链式反应 (RT-PCR) 证明，在所研究的间皮细胞和 MM 细胞中始终可检测到 B7-H3 mRNA；然而，实时定量 RT-PCR 分析显示，所研究的 MM 细胞中 B7-H3 mRNA 水平存在高度异质性。 B7-H3 蛋白表达的分析表明，两种细胞类型的 B7-H3 表达水平相当。 DNA 低甲基化剂 5-aza-20-deoxycytidine 处理并未显着影响 MM 细胞中 B7-H3 mRNA 的表达。在体内，虽然 B7-H3 在上皮变体的所有 13 个肿瘤活检组织中均表达，并且在 54% 的病例中表达高水平，但在梭形型 MM 中很少检测到，其中 1/5 的活检组织弱表达 B7-H3。这些发现表明，B7-H3 是 MM 新免疫治疗策略的一个有前途的靶点，特别是上皮变异。 J.细胞。生理学。 226: 2595-2600, 2011。(C) 2010 Wiley-Liss, Inc.
No treatment prolongs the survival of malignant mesothelioma (MM) patients. Since MM elicits anti-tumor host's immune responses, immunotherapy represents a promising strategy for its control. Immunomodulatory antibodies against components of the B7 family of immunomodulatory molecules that regulate T cell activation are being investigated in human malignancies including MM. The expression of B7-H3, a new component of the B7 family was investigated in primary cultures of human mesothelial cells (HMC) and in MM cell lines by flow cytometry and molecular analyses, and in MM tissues by immunohistochemistry. The role of DNA hypomethylating agents in modulating levels of B7-H3 expression in MM cells was also studied. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that B7-H3 mRNA was consistently detectable in mesothelial and MM cells investigated; however, real-time quantitative RT-PCR analyses showed highly heterogeneous levels of B7-H3 mRNA among investigated MM cells. The analysis of B7-H3 protein expression indicated that comparable levels of B7-H3 were expressed on both cell types. Treatment with the DNA hypomethylating agent 5-aza-20-deoxycytidine did not significantly affect the expression of B7-H3 mRNA in MM cells. In vivo, while B7-H3 was expressed in all 13 tumor biopsies of the epithelial variant, with high levels in 54% of cases, it was rarely detectable in spindle type MM in which 1/5 biopsies weakly expressed B7-H3. These findings suggest that B7-H3 is a promising target for new immunotherapeutic strategies in MM, with particular emphasis in the epithelial variant. J. Cell. Physiol. 226: 2595-2600, 2011. (C) 2010 Wiley-Liss, Inc.