Sialic Acid-Dependent Inhibition of T Cells by Exosomal Ganglioside GD3 in Ovarian Tumor Microenvironments.
Sialic Acid-Dependent Inhibition of T Cells by Exosomal Ganglioside GD3 in Ovarian Tumor Microenvironments.
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DOI：
10.4049/jimmunol.1801041
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发表时间：
2018-12-15
期刊：
影响因子：
--
通讯作者：
Bankert RB
中科院分区：
文献类型：
--
作者：
Shenoy GN;Loyall J;Berenson CS;Kelleher RJ Jr;Iyer V;Balu-Iyer SV;Odunsi K;Bankert RB
肿瘤微环境受到多种细胞和非细胞因子的免疫抑制，这些因子代表着潜在的癌症治疗靶点。虽然以前从卵巢肿瘤腹水中分离出的外切体可以引起快速和可逆的T细胞停滞，但存在于外切体上或存在于外切体内的免疫抑制因子还没有完全确定。在这里，我们确定GD3，一种表达在从人卵巢肿瘤腹水中分离的外体表面的神经节苷脂，与通过其T细胞受体激活的T细胞的功能停滞有关。这种停滞可通过抗体阻断外体GD3或移除外体GD3+来抑制。在表面表达GD3的空脂质体也抑制T细胞的激活，证实GD3有助于T细胞的功能停滞，而不受外体中存在的因素的影响。最后，我们证明了GD3介导的TCR激活的抑制依赖于唾液酸基，因为它们被酶从外切体或脂质体中移除会导致抑制能力的丧失。总体而言，这些数据将GD3定义为潜在的免疫治疗靶点。
The tumor microenvironment is rendered immunosuppressive by a variety of cellular and acellular factors, which represent potential cancer therapeutic targets. While exosomes isolated from ovarian tumor ascites fluids have been previously reported to induce a rapid and reversible T cell arrest, the factors present on or within exosomes that contribute to immunosuppression have not been fully defined. Here, we establish that GD3, a ganglioside expressed on the surface of exosomes isolated from human ovarian tumor ascites fluids, is causally linked to the functional arrest of T cells activated through their T cell receptor. This arrest is inhibited by antibody blockade of exosomal GD3 or by the removal of GD3+ exosomes. Empty liposomes expressing GD3 on the surface also inhibit the activation of T cells, establishing that GD3 contributes to the functional arrest of T cells, independent of factors present in exosomes. Finally, we demonstrate that the GD3-mediated arrest of the TCR activation is dependent upon sialic acid groups, since their enzymatic removal from exosomes or liposomes results in a loss of inhibitory capacity. Collectively, these data define GD3 as a potential immunotherapeutic target.
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DOI：
10.1016/j.ymeth.2015.04.014
发表时间：
2015-10-01
期刊：
Methods (San Diego, Calif.)
影响因子：
--
作者：
Lydic TA;Townsend S;Adda CG;Collins C;Mathivanan S;Reid GE
通讯作者：
Reid GE
影响因子：
4.3
作者：
Berenson, Charles S.;Nawar, Hesham F.;Connell, Terry D.
通讯作者：
Connell, Terry D.
DOI：
10.1038/nri3622
发表时间：
2014-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.5
作者：
Lo, Agnes S. Y.;Ma, Qiangzhong;Junghans, Richard P.
通讯作者：
Junghans, Richard P.
影响因子：
10.1
作者：
Kelleher RJ Jr;Balu-Iyer S;Loyall J;Sacca AJ;Shenoy GN;Peng P;Iyer V;Fathallah AM;Berenson CS;Wallace PK;Tario J;Odunsi K;Bankert RB
通讯作者：
Bankert RB