Department of Gene Vectors, Helmholtz Center, Marchioninistrasse 25, Munich, Germany.
Cancer Immunol Immunother. 2011 May;60(5):639-48. doi: 10.1007/s00262-011-0979-5. Epub 2011 Feb 4.
In order to grow within an immunocompetent host, tumour cells have evolved various strategies to cope with the host's immune system. These strategies include the downregulation of surface molecules and the secretion of immunosuppressive factors like IL-10 and PGE2 that impair the maturation of immune effector cells, among other mechanisms. Recently, tumour exosomes (TEX) have also been implicated in tumour-induced immune suppression as it has been shown that TEX can induce apoptosis in T lymphocytes. In this study, we extend our knowledge about immunosuppressive features of these microvesicles in that we show that TEX efficiently bind and sequester tumour-reactive antibodies and dramatically reduce their binding to tumour cells. Moreover, we demonstrate that this antibody sequestration reduces the antibody-dependent cytotoxicity by immune effector cells, which is among the most important anti-tumour reactions of the immune system and a significant activity of therapeutic antibodies. Taken together, these data point to the fact that tumour-derived exosomes interfere with the tumour-specific function of immune cells and constitute an additional mechanism how tumours escape from immune surveillance.
为了在免疫功能健全的宿主中生长，肿瘤细胞已经进化出各种策略来应对宿主的免疫系统。这些策略包括下调表面分子和分泌免疫抑制因子，如 IL-10 和 PGE2，这些因子会损害免疫效应细胞的成熟，以及其他机制。最近，肿瘤细胞外囊泡（TEX）也被牵连到肿瘤诱导的免疫抑制中，因为已经表明 TEX 可以诱导 T 淋巴细胞凋亡。在这项研究中，我们扩展了对这些微囊泡免疫抑制特征的认识，表明 TEX 能够有效地结合和隔离肿瘤反应性抗体，并显著降低它们与肿瘤细胞的结合。此外，我们证明这种抗体隔离降低了免疫效应细胞的抗体依赖性细胞毒性，这是免疫系统最重要的抗肿瘤反应之一，也是治疗性抗体的重要活性。综上所述，这些数据表明，肿瘤来源的外囊泡干扰了免疫细胞的肿瘤特异性功能，是肿瘤逃避免疫监视的另一种机制。
