Suppression of tumor formation in lymph nodes by L-selectin-mediated natural killer cell recruitment.
Suppression of tumor formation in lymph nodes by L-selectin-mediated natural killer cell recruitment.
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DOI：
10.1084/jem.20051473
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发表时间：
2005-12-19
期刊：
影响因子：
--
通讯作者：
Fukuda M
中科院分区：
文献类型：
--
作者：
Chen S;Kawashima H;Lowe JB;Lanier LL;Fukuda M
已知自然杀伤(NK)细胞在体内对某些肿瘤具有排斥作用；然而，NK细胞阻止肿瘤转移到次级淋巴器官的能力尚未得到解决。在这里，我们报告了在荷瘤宿主中，野生型小鼠的NK细胞被招募到区域淋巴结，但在缺乏L-选择素或L-选择素配体的小鼠中没有。通过过继转移和完全弗氏佐剂刺激实验，我们证明NK细胞上的L-选择素和内皮细胞上的L-选择素配体是NK细胞向淋巴结募集所必需的。此外，新鲜分离的常驻淋巴结NK细胞有效地溶解了肿瘤，在野生型或RAG-1缺陷小鼠中，B16黑色素瘤细胞向引流淋巴结的转移受到抑制，但当NK细胞被耗尽时，B16黑色素瘤细胞的转移受到抑制。虽然L-选择素缺陷的NK细胞在体外能有效地杀伤肿瘤细胞，但在L-选择素或L-选择素配体缺乏的小鼠中，由于NK细胞向淋巴结募集不足，对肿瘤转移的依赖抑制作用减弱。此外，用野生型NK细胞重组的L选择素缺陷小鼠的肿瘤转移受到显著抑制。这些结果表明，L-选择素介导的NK细胞募集在控制肿瘤向次级淋巴器官转移中起着关键作用。
Natural killer (NK) cells are known to reject certain tumors in vivo; however, the ability of NK cells to prevent metastasis of tumors into secondary lymphoid organs has not been addressed. Here, we report that in tumor-bearing hosts, NK cells are recruited to regional lymph nodes in wild-type mice, but not in mice deficient for L-selectin or L-selectin ligands. By adoptive transfer and complete Freund's adjuvant stimulation experiments, we demonstrated that L-selectin on NK cells and L-selectin ligands on endothelial cells are essential for NK cell recruitment to lymph nodes. Furthermore, freshly isolated resident lymph node NK cells lysed tumors efficiently, and metastasis of B16 melanoma cells to draining lymph nodes was suppressed in wild-type or Rag-1–deficient mice, but not when NK cells were depleted. Although L-selectin–deficient NK cells efficiently lysed tumor cells in vitro, NK cell–dependent suppression of tumor metastasis was diminished in mice deficient for L-selectin or L-selectin ligands because of insufficient NK cell recruitment to lymph nodes. Moreover, tumor metastasis was substantially inhibited in L-selectin–deficient mice reconstituted with wild-type NK cells. These findings indicate that L-selectin–mediated NK cell recruitment plays a crucial role in the control of tumor metastasis into secondary lymphoid organs.
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DOI：
10.1084/jem.191.1.129
发表时间：
2000-01-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Glas R;Franksson L;Une C;Eloranta ML;Ohlén C;Orn A;Kärre K
通讯作者：
Kärre K
DOI：
10.1073/pnas.040569797
发表时间：
2000-03-28
影响因子：
11.1
作者：
André, P;Spertini, O;Vivier, E
通讯作者：
Vivier, E
影响因子：
5.4
作者：
JULIUS, MH;SIMPSON, E;HERZENBERG, LA
通讯作者：
HERZENBERG, LA
DOI：
10.1073/pnas.201238598
发表时间：
2001-09-25
影响因子：
11.1
作者：
Cerwenka, A;Baron, JL;Lanier, LL
通讯作者：
Lanier, LL
影响因子：
20.3
作者：
Fehniger, TA;Cooper, MA;Caligiuri, MA
通讯作者：
Caligiuri, MA