Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack.
Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack.
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DOI：
10.1016/j.immuni.2015.01.010
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发表时间：
2015-02-17
期刊：
影响因子：
32.4
通讯作者：
Mandelboim, Ofer
中科院分区：
文献类型：
--
作者：
Gur, Chamutal;Ibrahim, Yara;Isaacson, Batya;Yamin, Rachel;Abed, Jawad;Gamliel, Moriya;Enk, Jonatan;Bar-On, Yotam;Stanietsky-Kaynan, Noah;Coppenhagen-Glazer, Shunit;Shussman, Noam;Almogy, Gideon;Cuapio, Angelica;Hofer, Erhard;Mevorach, Dror;Tabib, Adi;Ortenberg, Rona;Markel, Gal;Miklic, Karmela;Jonjic, Stipan;Brennan, Caitlin A.;Garrett, Wendy S.;Bachrach, Gilad;Mandelboim, Ofer
肿瘤微环境中存在细菌，如具核梭杆菌。然而，肿瘤内细菌的免疫后果仍不清楚。在这里，我们已经表明，自然杀伤（NK）细胞杀死各种肿瘤的抑制存在各种F。具核菌株我们的数据支持这种F.核酸介导的抑制由人而非小鼠TIGIT介导，TIGIT是存在于所有人NK细胞和各种T细胞上的抑制性受体。利用F. nucleatum突变体中，我们发现F. nucleatum直接与TIGIT相互作用，导致NK细胞细胞毒性的抑制。我们已经进一步证明，肿瘤浸润淋巴细胞表达TIGIT，并且T细胞活性也被F.通过Fap2的核质。我们的研究结果确定了一种细菌依赖的肿瘤免疫逃避机制，其中肿瘤利用F.核质通过TIGIT抑制免疫细胞活性。
Bacteria, such as Fusobacterium nucleatum, are present in the tumor microenvironment. However, the immunological consequences of intra-tumoral bacteria remain unclear. Here, we have shown that natural killer (NK) cell killing of various tumors is inhibited in the presence of various F. nucleatum strains. Our data support that this F. nucleatum-mediated inhibition is mediated by human, but not by mouse TIGIT, an inhibitory receptor present on all human NK cells and on various T cells. Using a library of F. nucleatum mutants, we found that the Fap2 protein of F. nucleatum directly interacted with TIGIT, leading to the inhibition of NK cell cytotoxicity. We have further demonstrated that tumor-infiltrating lymphocytes expressed TIGIT and that T cell activities were also inhibited by F. nucleatum via Fap2. Our results identify a bacterium-dependent, tumor-immune evasion mechanism in which tumors exploit the Fap2 protein of F. nucleatum to inhibit immune cell activity via TIGIT.
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影响因子：
20.3
作者：
Elias S;Yamin R;Golomb L;Tsukerman P;Stanietsky-Kaynan N;Ben-Yehuda D;Mandelboim O
通讯作者：
Mandelboim O
影响因子：
4.9
作者：
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通讯作者：
Allen-Vercoe, Emma
影响因子：
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作者：
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通讯作者：
Holt, Robert A.
影响因子：
30.3
作者：
Rubinstein MR;Wang X;Liu W;Hao Y;Cai G;Han YW
通讯作者：
Han YW