p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells.
p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells.
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DOI：
10.1084/jem.20130783
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发表时间：
2013-09-23
期刊：
影响因子：
--
通讯作者：
Raulet DH
中科院分区：
文献类型：
--
作者：
Iannello A;Thompson TW;Ardolino M;Lowe SW;Raulet DH
P53的诱导通过CCL2调节NK细胞的招募，导致NKG2D依赖的衰老肿瘤的消除。诱导细胞衰老是P53抑制肿瘤发生的重要机制。使用小鼠肝癌模型，其中细胞衰老是由可诱导的p53表达在体内触发的，我们证明了NK细胞参与了衰老肿瘤的消除。衰老肿瘤细胞的消除依赖于NKG2D。有趣的是，P53的修复既不会增加配体的表达，也不会增加NK细胞对裂解的敏感性。相反，P53的修复导致肿瘤细胞分泌各种趋化因子，有可能招募NK细胞。抗体中和CCL2，而不是CCL3、CCL4或CCL5，可阻止NK细胞向衰老肿瘤募集并减少其清除。我们的发现表明，NK细胞消除衰老肿瘤是与调节NK细胞募集的P53表达或衰老相关的信号和其他诱导肿瘤细胞上NKG2D配体表达的信号协同作用的结果。
p53 induction regulates NK cell recruitment via CCL2, leading to NKG2D-dependent elimination of senescent tumors. The induction of cellular senescence is an important mechanism by which p53 suppresses tumorigenesis. Using a mouse model of liver carcinoma, where cellular senescence is triggered in vivo by inducible p53 expression, we demonstrated that NK cells participate in the elimination of senescent tumors. The elimination of senescent tumor cells is dependent on NKG2D. Interestingly, p53 restoration neither increases ligand expression nor increases the sensitivity to lysis by NK cells. Instead, p53 restoration caused tumor cells to secrete various chemokines with the potential to recruit NK cells. Antibody-mediated neutralization of CCL2, but not CCL3, CCL4 or CCL5, prevented NK cell recruitment to the senescent tumors and reduced their elimination. Our findings suggest that elimination of senescent tumors by NK cells occurs as a result of the cooperation of signals associated with p53 expression or senescence, which regulate NK cell recruitment, and other signals that induce NKG2D ligand expression on tumor cells.
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影响因子：
78.5
作者：
Collado, Manuel;Serrano, Manuel
通讯作者：
Serrano, Manuel
影响因子：
11.2
作者：
Bavik, C;Coleman, I;Nelson, PS
通讯作者：
Nelson, PS
DOI：
10.1158/1078-0432.ccr-09-0991
发表时间：
2009-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
McGilvray RW;Eagle RA;Watson NF;Al-Attar A;Ball G;Jafferji I;Trowsdale J;Durrant LG
通讯作者：
Durrant LG
影响因子：
5.4
作者：
Diefenbach, A;Hsia, JK;Raulet, DH
通讯作者：
Raulet, DH
影响因子：
64.8
作者：
Kang, Tae-Won;Yevsa, Tetyana;Zender, Lars
通讯作者：
Zender, Lars