Beccard Inga J, Hofmann Linda, Schroeder Jan C, Ludwig Sonja, Laban Simon, Brunner Cornelia, Lotfi Ramin, Hoffmann Thomas K, Jackson Edwin K, Schuler Patrick J, Theodoraki Marie-Nicole
Department of Otorhinolaryngology, Head and Neck Surgery, University of Ulm, 89070 Ulm, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, 68167 Mannheim, Germany.
Cancers (Basel). 2020 Jul 21;12(7):1997. doi: 10.3390/cancers12071997.
Plasma-derived exosomes of head and neck squamous cell carcinoma (HNSCC) patients carry inhibitory factors mediating immune suppression. Separation of tumor-derived exosomes (TEX) and non-TEX may assist in a better understanding of their respective parental cells. Here, we evaluate the impact of TEX or hematopoietic-derived exosomes on immune suppression. We evaluated apoptosis in CD8+ T cells, conversion of CD4+ T cells to regulatory T cells (T), and adenosine production by TEX, non-TEX, or total exosomes. Exosome protein cargo was significantly higher in total and CD45(-) exosomes from high stage compared to low stage patients. Furthermore, total and CD45(-) exosomes of high stage patients induced more apoptosis in CD8+ T cells than their low stage counterparts. CD69 suppression, a marker of reduced CD8+ T cell activation, was only mediated by CD45(-) exosomes. All fractions induced T differentiation, defined by CD39 expression, but only CD45(-) exosomes showed a stage-dependent conversion. CD45(-) exosomes produced higher adenosine concentrations than CD45(+) exosomes, concluding that adenosine production measured in total exosomes mainly derives from TEX. The presented results show significant induction of immune suppression by TEX in HNSCC. This immunosuppressive effect supports the potential role of exosomes as liquid biomarkers for disease stage and level of immune suppression.
头颈部鳞状细胞癌（HNSCC）患者的血浆来源外泌体携带介导免疫抑制的抑制因子。分离肿瘤来源的外泌体（TEX）和非TEX可能有助于更好地了解它们各自的亲代细胞。在此，我们评估TEX或造血来源的外泌体对免疫抑制的影响。我们评估了CD8+T细胞中的细胞凋亡、CD4+T细胞向调节性T细胞（T）的转化以及TEX、非TEX或总外泌体产生的腺苷。与低分期患者相比，高分期患者的总外泌体和CD45（-）外泌体中的外泌体蛋白含量显著更高。此外，高分期患者的总外泌体和CD45（-）外泌体比低分期患者的外泌体在CD8+T细胞中诱导更多的细胞凋亡。CD69抑制是CD8+T细胞活化降低的标志物，仅由CD45（-）外泌体介导。所有组分均诱导由CD39表达定义的T细胞分化，但只有CD45（-）外泌体显示出阶段依赖性转化。CD45（-）外泌体产生的腺苷浓度高于CD45（+）外泌体，得出总外泌体中测量的腺苷产生主要来自TEX的结论。所呈现的结果表明HNSCC中TEX对免疫抑制有显著诱导作用。这种免疫抑制作用支持外泌体作为疾病阶段和免疫抑制水平的液体生物标志物的潜在作用。
