Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles.
Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles.
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通过含有FASL的微泡的肿瘤细胞分泌诱导淋巴细胞凋亡。
DOI：
10.1084/jem.20011624
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发表时间：
2002-05-20
期刊：
影响因子：
--
通讯作者：
Fais S
中科院分区：
文献类型：
--
作者：
Andreola G;Rivoltini L;Castelli C;Huber V;Perego P;Deho P;Squarcina P;Accornero P;Lozupone F;Lugini L;Stringaro A;Molinari A;Arancia G;Gentile M;Parmiani G;Fais S
肿瘤细胞的 FasL 表达可能通过一种称为“Fas 肿瘤反击”的机制损害体内抗肿瘤免疫反应的功效这一假设最近受到质疑，并因相互矛盾的结果而成为激烈争论的对象。在这里，我们明确地表明，FasL 确实可以在黑色素瘤细胞的细胞质中检测到，并且其表达仅限于含有黑色素体的多泡体。在这些结构中，FasL 与黑素体（即 gp100）和溶酶体（即 CD63）抗原共定位。通过蛋白质印迹和细胞荧光测定法检测到，分离的黑素体表达 FasL，并且它们可以在 Jurkat 细胞中发挥 Fas 介导的细胞凋亡作用。我们还发现，含有黑素体的多泡体在细胞外脱粒并释放带有 FasL 的微泡，这些微泡共表达 gp100 和 CD63 并保留其触发 Fas 依赖性淋巴细胞凋亡的功能活性。因此，我们的数据为通过分泌表达功能性 FasL 的亚细胞颗粒来潜在地在 Fas 肿瘤反击中发挥作用的新机制提供了证据。这种囊泡可能形成一种前线，阻碍淋巴细胞和其他免疫活性细胞进入肿瘤病变并发挥其抗肿瘤活性。
The hypothesis that FasL expression by tumor cells may impair the in vivo efficacy of antitumor immune responses, through a mechanism known as ‘Fas tumor counterattack,’ has been recently questioned, becoming the object of an intense debate based on conflicting results. Here we definitely show that FasL is indeed detectable in the cytoplasm of melanoma cells and its expression is confined to multivesicular bodies that contain melanosomes. In these structures FasL colocalizes with both melanosomal (i.e., gp100) and lysosomal (i.e., CD63) antigens. Isolated melanosomes express FasL, as detected by Western blot and cytofluorimetry, and they can exert Fas-mediated apoptosis in Jurkat cells. We additionally show that melanosome-containing multivesicular bodies degranulate extracellularly and release FasL-bearing microvesicles, that coexpress both gp100 and CD63 and retain their functional activity in triggering Fas-dependent apoptosis of lymphoid cells. Hence our data provide evidence for a novel mechanism potentially operating in Fas tumor counterattack through the secretion of subcellular particles expressing functional FasL. Such vesicles may form a sort of front line hindering lymphocytes and other immunocompetent cells from entering neoplastic lesions and exert their antitumor activity.
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影响因子：
56.9
作者：
Hahne, M;Rimoldi, D;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
4.8
作者：
Jodo, S;Xiao, S;Ju, ST
通讯作者：
Ju, ST
DOI：
10.1084/jem.188.9.1717
发表时间：
1998-11-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Owen-Schaub LB;van Golen KL;Hill LL;Price JE
通讯作者：
Price JE
影响因子：
64.8
作者：
Irmler, M;Thome, M;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
4.4
作者：
Favre-Felix, N;Fromentin, A;Bonnotte, B
通讯作者：
Bonnotte, B