Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death.
Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death.
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DOI：
10.3389/fimmu.2015.00588
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发表时间：
2015
影响因子：
7.3
通讯作者：
Agostinis P
中科院分区：
文献类型：
--
作者：
Garg AD;Galluzzi L;Apetoh L;Baert T;Birge RB;Bravo-San Pedro JM;Breckpot K;Brough D;Chaurio R;Cirone M;Coosemans A;Coulie PG;De Ruysscher D;Dini L;de Witte P;Dudek-Peric AM;Faggioni A;Fucikova J;Gaipl US;Golab J;Gougeon ML;Hamblin MR;Hemminki A;Herrmann M;Hodge JW;Kepp O;Kroemer G;Krysko DV;Land WG;Madeo F;Manfredi AA;Mattarollo SR;Maueroder C;Merendino N;Multhoff G;Pabst T;Ricci JE;Riganti C;Romano E;Rufo N;Smyth MJ;Sonnemann J;Spisek R;Stagg J;Vacchelli E;Vandenabeele P;Vandenberk L;Van den Eynde BJ;Van Gool S;Velotti F;Zitvogel L;Agostinis P
最近，恶性细胞的免疫原性被认为是癌症治疗功效的关键决定因素。因此，除了开发直接免疫刺激方案（包括基于树突状细胞的疫苗、检查点阻断疗法和过继性 T 细胞转移）外，研究人员还开始关注肿瘤细胞的整体免疫生物学。现在很清楚，癌细胞可以通过经历一种特殊形式的细胞死亡来屈服于一些抗癌疗法，这种死亡形式的特点是由于所谓的“损伤相关分子模式”（DAMP）的发射而增加了免疫原性潜力。免疫原性细胞死亡 (ICD) 导致的细胞释放 DAMP 和其他免疫刺激因子，有利于与免疫系统建立有效的界面。这会引发针对肿瘤的免疫反应，从而消除残留的、耐药的癌细胞，并建立免疫记忆。尽管自 ICD 发现以来，ICD 的表征精度不断提高，但仍有几个问题有待解决。在这里，我们总结并列出了 ICD 的主要分子、免疫学、临床前和临床方面，试图抓住这一现象的本质，并确定这个快速扩展的研究领域的未来挑战。
The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called “damage-associated molecular patterns” (DAMPs). The emission of DAMPs and other immunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation.