Immunogenic tumor cell death promotes dendritic cell migration and inhibits tumor growth via enhanced T cell immunity.
Immunogenic tumor cell death promotes dendritic cell migration and inhibits tumor growth via enhanced T cell immunity.
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DOI：
10.1016/j.isci.2021.102424
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发表时间：
2021-05-21
期刊：
影响因子：
5.8
通讯作者：
Tomura M
中科院分区：
文献类型：
--
作者：
Moriya T;Kitagawa K;Hayakawa Y;Hemmi H;Kaisho T;Ueha S;Ikebuchi R;Yasuda I;Nakanishi Y;Honda T;Matsushima K;Kabashima K;Ueda M;Kusumoto Y;Chtanova T;Tomura M
免疫原性肿瘤细胞死亡增强抗肿瘤免疫。然而，这种效应背后的机制尚不完全清楚。我们在表达KikGR光转化蛋白的小鼠中建立了原位诱导肿瘤细胞死亡的系统，并利用活体光标记研究了其对树突状细胞（DC）迁移和T细胞应答的影响。我们证明肿瘤细胞死亡通过肿瘤浸润(Ti)- dc和HMGB1-TLR4和ATP-P2X7受体信号依赖的Ti- dc向引流淋巴结（dln）的迁移诱导肿瘤细胞吞噬。这导致记忆前体效应表型的抗肿瘤CD8+ T细胞增加，并以CD103+ dc依赖的方式抑制继发性肿瘤生长。然而，将诱导肿瘤细胞死亡与脂多糖联合处理可刺激Ti-DC成熟并向dln迁移，但不能提高肿瘤免疫力。因此，免疫原性肿瘤细胞死亡通过增加Ti-DC向dln的迁移来增强肿瘤免疫，从而促进抗肿瘤T细胞反应和肿瘤生长抑制。免疫原性细胞死亡（ICD）促进肿瘤浸润(Ti)- dc向dLNs的迁移ICD诱导Ti- dc向dLNs的迁移利用P2X7R和HMGB1信号通路LPS处理减弱ICD的抗肿瘤作用CD103+ dc在ICD时抑制继发性肿瘤生长免疫学；细胞生物学；癌症
Immunogenic tumor cell death enhances anti-tumor immunity. However, the mechanisms underlying this effect are incompletely understood. We established a system to induce tumor cell death in situ and investigated its effect on dendritic cell (DC) migration and T cell responses using intravital photolabeling in mice expressing KikGR photoconvertible protein. We demonstrate that tumor cell death induces phagocytosis of tumor cells by tumor-infiltrating (Ti)-DCs, and HMGB1-TLR4 and ATP-P2X7 receptor signaling-dependent Ti-DC emigration to draining lymph nodes (dLNs). This led to an increase in anti-tumor CD8+ T cells of memory precursor effector phenotype and secondary tumor growth inhibition in a CD103+ DC-dependent manner. However, combining tumor cell death induction with lipopolysaccharide treatment stimulated Ti-DC maturation and emigration to dLNs but did not improve tumor immunity. Thus, immunogenic tumor cell death enhances tumor immunity by increasing Ti-DC migration to dLNs where they promote anti-tumor T cell responses and tumor growth inhibition. Immunogenic cell death (ICD) promotes egress of tumor-infiltrating (Ti)-DCs to dLNs ICD induced Ti-DC migration to dLNs utilizes P2X7R and HMGB1 signaling pathways LPS treatment attenuates the anti-tumor effects of ICD CD103+ DCs are required at the time of ICD for suppression of secondary tumor growth Immunology ; Cell Biology ; Cancer
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影响因子：
5.8
作者：
Garg, Abhishek D.;Krysko, Dmitri V.;Agostinis, Patrizia
通讯作者：
Agostinis, Patrizia
靶向CD8 T细胞免疫的最新进展，以实现更有效的癌症免疫疗法。
影响因子：
7.3
作者：
Durgeau A;Virk Y;Corgnac S;Mami-Chouaib F
通讯作者：
Mami-Chouaib F
DOI：
10.1084/jem.20050915
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
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
通讯作者：
Kroemer G
鞘氨醇 1-磷酸受体 1 通过抑制外周组织 T 淋巴细胞进入传入淋巴管而导致组织滞留
影响因子：
30.5
作者：
Ledgerwood, Levi G.;Lal, Girdhari;Bromberg, Jonathan S.
通讯作者：
Bromberg, Jonathan S.
影响因子：
7.2
作者：
Kobayashi T;Doff BL;Rearden RC;Leggatt GR;Mattarollo SR
通讯作者：
Mattarollo SR