Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
Immunol Lett. 2012 Nov-Dec;148(1):34-8. doi: 10.1016/j.imlet.2012.07.006. Epub 2012 Aug 8.
To clarify controversies in the literature of the field, we have purified and characterized B16F1 melanoma cell derived exosomes (mcd-exosomes) then we attempted to dissect their immunological activities. We tested how mcd-exosomes influence CD4+ T cell proliferation induced by bone marrow derived dendritic cells; we quantified NF-κB activation in mature macrophages stimulated with mcd-exosomes, and we compared the cytokine profile of LPS-stimulated, IL-4 induced, and mcd-exosome treated macrophages. We observed that mcd-exosomes helped the maturation of dendritic cells, enhancing T cell proliferation induced by the treated dendritic cells. The exosomes also activated macrophages, as measured by NF-κB activation. The cytokine and chemokine profile of macrophages treated with tumor cell derived exosomes showed marked differences from those induced by either LPS or IL-4, and it suggested that exosomes may play a role in the tumor progression and metastasis formation through supporting tumor immune escape mechanisms.
为了澄清该领域文献中的争议，我们纯化并鉴定了 B16F1 黑色素瘤细胞衍生的外泌体（mcd-exosomes），然后尝试剖析其免疫学活性。我们测试了 mcd-exosomes 如何影响骨髓来源的树突状细胞诱导的 CD4+T 细胞增殖；我们量化了成熟巨噬细胞受 mcd-exosomes 刺激后 NF-κB 的激活情况，并比较了 LPS 刺激、IL-4 诱导和 mcd-exosome 处理的巨噬细胞的细胞因子谱。我们观察到 mcd-exosomes 有助于树突状细胞的成熟，增强了经处理的树突状细胞诱导的 T 细胞增殖。外泌体还通过 NF-κB 激活激活了巨噬细胞。与 LPS 或 IL-4 诱导的细胞因子和趋化因子谱相比，用肿瘤细胞衍生的外泌体处理的巨噬细胞的细胞因子和趋化因子谱显示出明显差异，这表明外泌体可能通过支持肿瘤免疫逃逸机制在肿瘤进展和转移形成中发挥作用。
