Tumor Expression of CD83 Reduces Glioma Progression and Is Associated with Reduced Immunosuppression.

IF 2 Q3 ONCOLOGY
Malcolm F McDonald, Rachel Naomi Curry, Isabella O'Reilly, Brittney Lozzi, Alexis Cervantes, Zhung-Fu Lee, Anna Rosenbaum, Peihao He, Carrie Mohila, Arif O Harmanci, Akdes Serin Harmanci, Benjamin Deneen, Ganesh Rao
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Abstract

Significance: Immunosuppression in malignant glioma remains a barrier to therapeutic development. CD83 overexpression in human and mouse glioma increases survival. CD83+ tumor cells promote signatures related to cytotoxic T cells, enhanced activation of CD8+ T cells, and increased proinflammatory cytokines. These findings suggest that tumor-expressed CD83 could mediate tumor-immune communications.

肿瘤表达 CD83 可减少胶质瘤的进展,并与免疫抑制的减少有关。
恶性胶质瘤是致死率最高的脑癌,其免疫抑制微环境阻碍了肿瘤细胞的清除,妨碍了免疫治疗干预。尽管在描述癌症的细胞和细胞外特征方面取得了进展,但人们对胶质瘤特有的免疫抑制机制仍然知之甚少。我们对胶质瘤样本进行了单细胞 RNA 测序,结果发现人类和小鼠胶质瘤细胞中有一部分表达 CD83,这是一种与成熟抗原递呈细胞(APCs)相关的标记。为了研究肿瘤细胞 CD83 表达对胶质瘤预后的影响,我们采用了免疫功能健全的胶质瘤小鼠模型、人类样本的生物信息学分析和体外试验。我们的研究结果表明,CD83+肿瘤细胞有助于抑制肿瘤生长,并与增强的细胞毒性T细胞特征和活化的CD8+T细胞有关。在 CD83 表达过高的肿瘤中发现了增加的促炎细胞因子,这也与 CD8+ 的长期抗肿瘤反应相关。重要的是,肿瘤衍生的 CD83 可以介导与 T 细胞的交流,改变免疫微环境,从而增强与免疫相关的肿瘤清除能力。总之,我们的数据表明,肿瘤细胞表达的CD83支持恶性胶质瘤中内源性抗肿瘤T细胞的构成。未来的研究工作可能会进一步探讨 CD83 的表达是否能增强免疫治疗方法并改善患者预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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