Exosomes and the MICA-NKG2D system in cancer
Exosomes and the MICA-NKG2D system in cancer
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DOI：
10.1016/j.bcmd.2005.03.003
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发表时间：
2005-05-01
影响因子：
2.3
通讯作者：
Tabi, Z
中科院分区：
文献类型：
--
作者：
Clayton, A;Tabi, Z
胞外体是一种纳米大小的囊泡，由多种细胞类型分泌，其生物学功能尚不明确。几个小组已经证明了操纵外切体来激活细胞免疫反应的潜力。然而，外切体可能抑制免疫反应的可能性还没有得到广泛的解决。我们已经研究了肿瘤细胞产生的外切体是否可以通过调节效应细胞的NKG2D受体的表达来抑制免疫功能。肿瘤外切体与新鲜外周血白细胞孵育后，NKG2D阳性的CD3+CD8+细胞和CD3-细胞的比例显著降低48it。这种效应是剂量依赖的，并在包括乳腺癌和间皮瘤在内的不同肿瘤细胞的外切体中表现出来。肿瘤外切体表型分析显示，几种NKG2D配体呈阳性表达，抗体阻断实验揭示了这些配体在驱动NKG2D阳性效应细胞比例下降中的重要性。例如，与肿瘤外切体预先孵育的CD8+T细胞株杀伤肽冲击的T2靶细胞的能力显着降低。这些数据突显了携带NKG2D配体的Turner外切体作为一种机制在癌症免疫逃避中的作用。2005 Elsevier Inc.保留所有权利。
Exosomes are nanometer sized vesicles, secreted by a diverse range of cell types, whose biological functions rem ambiguous. Several groups have demonstrated the potential of manipulating exosomes for activating cellular immune responses. The possibility that exosomes may inhibit immunological responses, however, has not been widely addressed.We have investigated if exosomes produced by tumor cells can inhibit immunological functions, through modulating expression of the NKG2D) receptor by effector cells. Incubating tumor exosomes with fresh peripheral blood leukocytes resulted in a marked reduction in the proportion of NKG2D-positive CD3+ CD8+ Cells, and CD3- cells by 48 It. This effect was dose dependent and was shown with exosomes from different tumor cells including breast cancer and mesothelioma.Analysis of tumor exosome-phenotype revealed positive expression of several NKG2D ligands, and antibody blocking experiments revealed the importance of such ligands in driving the reduction in the proportion of NKG2D-positive effector cells.The functional importance of the decrease in NKG2D-positive cells was addressed in vitro cytotoxicity assays. For example a CD8+ T cell line pre-incubated with tumor exosomes had significant decreased capacity to kill peptide-pulsed T2 target cells.These data highlight a role for turner exosomes bearing NKG2D ligands as a mechanism contributing to cancer immune evasion. 2005 Elsevier Inc. All rights reserved.