Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death.
Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death.
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DOI：
10.1084/jem.20050915
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发表时间：
2005-12-19
期刊：
影响因子：
--
通讯作者：
Kroemer G
中科院分区：
文献类型：
--
作者：
Casares N;Pequignot MO;Tesniere A;Ghiringhelli F;Roux S;Chaput N;Schmitt E;Hamai A;Hervas-Stubbs S;Obeid M;Coutant F;Métivier D;Pichard E;Aucouturier P;Pierron G;Garrido C;Zitvogel L;Kroemer G
全身抗癌化疗是免疫抑制性的，并且主要诱导非免疫原性肿瘤细胞死亡。在这里，我们表明，即使在没有任何佐剂的情况下，肿瘤细胞死亡的蒽环类抗生素可以引起一个有效的抗肿瘤免疫反应，抑制接种肿瘤的生长或导致建立瘤的消退。虽然蒽环类抗生素和丝裂霉素C都能诱导凋亡，但只有蒽环类抗生素诱导的免疫原性细胞死亡具有免疫原性。通过Z-VAD-fetamine或用杆状病毒抑制剂p35转染的半胱天冬酶抑制剂不能抑制多柔比星（DX）诱导的细胞死亡，但抑制了几种啮齿动物肿瘤模型中垂死肿瘤细胞的免疫原性。树突状细胞（DC）或CD 8 +T细胞的耗竭在体内消除了针对DX处理的凋亡肿瘤细胞的免疫应答。半胱天冬酶抑制剂抑制DX-杀死的细胞被DC吞噬的能力，但对它们诱导DC成熟的能力没有影响。新鲜切除的肿瘤在体外DX治疗后变得具有免疫原性，并且DX的瘤内接种可以引发免疫活性小鼠中建立的肿瘤的消退。这些结果描绘了一个程序的癌症疫苗的产生和刺激体内抗肿瘤免疫反应。
Systemic anticancer chemotherapy is immunosuppressive and mostly induces nonimmunogenic tumor cell death. Here, we show that even in the absence of any adjuvant, tumor cells dying in response to anthracyclins can elicit an effective antitumor immune response that suppresses the growth of inoculated tumors or leads to the regression of established neoplasia. Although both antracyclins and mitomycin C induced apoptosis with caspase activation, only anthracyclin-induced immunogenic cell death was immunogenic. Caspase inhibition by Z-VAD-fmk or transfection with the baculovirus inhibitor p35 did not inhibit doxorubicin (DX)-induced cell death, yet suppressed the immunogenicity of dying tumor cells in several rodent models of neoplasia. Depletion of dendritic cells (DCs) or CD8+T cells abolished the immune response against DX-treated apoptotic tumor cells in vivo. Caspase inhibition suppressed the capacity of DX-killed cells to be phagocytosed by DCs, yet had no effect on their capacity to elicit DC maturation. Freshly excised tumors became immunogenic upon DX treatment in vitro, and intratumoral inoculation of DX could trigger the regression of established tumors in immunocompetent mice. These results delineate a procedure for the generation of cancer vaccines and the stimulation of anti-neoplastic immune responses in vivo.
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影响因子：
32.4
作者：
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通讯作者：
Lang, RA
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4.4
作者：
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20.3
作者：
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影响因子：
8
作者：
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通讯作者：
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