DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells
DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells
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DOI：
10.1158/0008-5472.can-06-2264
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发表时间：
2007-02-01
期刊：
影响因子：
11.2
通讯作者：
Malmberg, Karl Johan
中科院分区：
文献类型：
--
作者：
Carlsten, Mattias;Bjorkstrom, Niklas K.;Malmberg, Karl Johan
尽管自然杀伤（NK）细胞以其杀死肿瘤的能力而闻名，但很少有研究涉及静息（未活化）NK细胞与新鲜分离的人类肿瘤之间的相互作用。在这里，我们表明，人类白细胞抗原I类低的肿瘤细胞直接从晚期卵巢癌患者分离触发脱粒的休息同种异体NK细胞。这通过诱导肿瘤细胞中颗粒酶B和caspase-6活性以及显著的肿瘤细胞溶解来证实。卵巢癌细胞显示DNA辅助分子-1（DNAM-1）配体PVB的普遍表达以及NKG 2D配体MICA/MICB和ULBP 1、ULBP 2和ULBP 3的稀疏/异质表达。与NK受体配体表达谱一致，抗体介导的受体激活途径的阻断揭示了DNAM-1的主导作用以及NKG 2D信号传导在肿瘤细胞识别中的补充贡献。这些结果表明，静息NK细胞能够直接识别新鲜分离的人肿瘤细胞，并将卵巢癌鉴定为基于过继NK细胞的免疫治疗的潜在靶点。
Although natural killer (NK) cells are well known for their ability to kill tumors, few studies have addressed the interactions between resting (nonactivated) NK cells and freshly isolated human tumors. Here, we show that human leukocyte antigen class I-low tumor cells isolated directly from patients with advanced ovarian carcinoma trigger degranulation by resting allogeneic NK cells. This was paralleled by induction of granzyme B and caspase-6 activities in the tumor cells and significant tumor cell lysis. Ovarian carcinoma cells displayed ubiquitous expression of the DNAX accessory molecule-1 (DNAM-1) ligand PVB and sparse/heterogeneous expression of the NKG2D ligands MICA/MICB and ULBP1, ULBP2, and ULBP3. In line with the NK receptor ligand expression profiles, antibody-mediated blockade of activating receptor pathways revealed a dominant role for DNAM-1 and a complementary contribution of NKG2D signaling in tumor cell recognition. These results show that resting NK cells are capable of directly recognizing freshly isolated human tumor cells and identify ovarian carcinoma as a potential target for adoptive NK cell-based immunotherapy.