Inhibition of phosphatidylserine recognition heightens the immunogenicity of irradiated lymphoma cells in vivo.
Inhibition of phosphatidylserine recognition heightens the immunogenicity of irradiated lymphoma cells in vivo.
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抑制磷脂酰丝氨酸识别可增强体内受辐射淋巴瘤细胞的免疫原性。
DOI：
10.1084/jem.20040327
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发表时间：
2004-11-01
影响因子：
15.3
通讯作者：
Herrmann, M
中科院分区：
文献类型：
--
作者：
Bondanza, A;Zimmermann, VS;Rovere-Querini, P;Turnay, J;Dumitriu, IE;Stach, CM;Voll, RE;Gaipl, US;Bertling, W;Pöschl, E;Kalden, JR;Manfredi, AA;Herrmann, M
迫切需要提高肿瘤免疫原性的策略。尽管用受辐射死亡的淋巴瘤细胞接种疫苗能激发肿瘤特异性免疫反应，但其作为免疫原的效率很低。膜联蛋白V(AxV)与凋亡和坏死细胞表面的磷脂酰丝氨酸具有高亲和力，从而损害巨噬细胞对其的摄取。在这里，我们报告AxV优先靶向受照射的淋巴瘤细胞到CD8+树突状细胞进行体内清除，诱导促炎细胞因子的释放，并显著增强对肿瘤的保护。这种反应既具有记忆性，因为受保护的动物在72天后拒绝活的淋巴瘤细胞，也具有特异性，因为接种疫苗的动物未能排斥无关的肿瘤。最后，AxV偶联照射的细胞诱导生长的肿瘤消退。这些数据表明，可以利用与垂死的肿瘤细胞结合的内源性佐剂来靶向肿瘤进行免疫排斥。
Strategies to enhance the immunogenicity of tumors are urgently needed. Although vaccination with irradiated dying lymphoma cells recruits a tumor-specific immune response, its efficiency as immunogen is poor. Annexin V (AxV) binds with high affinity to phosphatidylserine on the surface of apoptotic and necrotic cells and thereby impairs their uptake by macrophages. Here, we report that AxV preferentially targets irradiated lymphoma cells to CD8+ dendritic cells for in vivo clearance, elicits the release of proinflammatory cytokines and dramatically enhances the protection elicited against the tumor. The response was endowed with both memory, because protected animals rejected living lymphoma cells after 72 d, and specificity, because vaccinated animals failed to reject unrelated neoplasms. Finally, AxV–coupled irradiated cells induced the regression of growing tumors. These data indicate that endogenous adjuvants that bind to dying tumor cells can be exploited to target tumors for immune rejection.
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影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
4.4
作者：
Ferguson, TA;Herndon, J;Green, DR
通讯作者：
Green, DR
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
12.4
作者：
Krahling, S;Callahan, MK;Schlegel, RA
通讯作者：
Schlegel, RA
影响因子：
12.4
作者：
Callahan, MK;Williamson, P;Schlegel, RA
通讯作者：
Schlegel, RA