KIR2DS2 Expression Identifies NK Cells With Enhanced Anticancer Activity.
KIR2DS2 Expression Identifies NK Cells With Enhanced Anticancer Activity.
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DOI：
10.4049/jimmunol.2101139
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发表时间：
2022-07-15
期刊：
影响因子：
--
通讯作者：
Khakoo SI
中科院分区：
文献类型：
--
作者：
Blunt MD;Vallejo Pulido A;Fisher JG;Graham LV;Doyle ADP;Fulton R;Carter MJ;Polak M;Johnson PWM;Cragg MS;Forconi F;Khakoo SI
自然杀伤细胞(NK细胞)是治疗血液病和实体肿瘤的一种很有前途的细胞疗法。免疫遗传学研究发现，多种激活的杀伤细胞免疫球蛋白样受体(KIR)与肿瘤预后有关。具体地说，KIR2DS2与血液系统恶性肿瘤移植后复发率的降低和实体肿瘤的预后改善有关，但其机制仍不清楚。因此，我们研究了KIR2DS2的表达对NK细胞功能的影响。利用一种新型的流式细胞仪组件，我们发现高表达KIR2DS2的人NK细胞对恶性B细胞系、肝癌细胞系和原代慢性淋巴细胞白血病(CLL)细胞的自发激活作用增强。KIR2DS2高NK细胞表面CD16表达增加，相应地，KIR2DS2高NK细胞对临床相关抗CD20抗体美妥昔单抗和奥昔单抗包被的淋巴瘤细胞的杀伤活性增强。批量RNA测序显示，KIR2DS2高表达的NK细胞上调了NK介导的细胞毒作用、翻译和FCGR基因途径。我们开发了一种新的单细胞RNA测序技术来鉴定KIR2DS2+NK细胞，这证实了KIR2DS2与增强的NK细胞介导的细胞毒作用有关。这项研究提供的证据表明，KIR2DS2标记了一组具有抗癌活性的NK细胞，并表明KIR2DS2是基于NK的治疗策略的一个有吸引力的靶点。
Natural killer (NK) cells are promising cellular therapeutics against haematological and solid malignancies. Immunogenetic studies have identified that various activating killer cell immunoglobulin-like receptors (KIR) are associated with cancer outcomes. Specifically, KIR2DS2 has been associated with reduced incidence of relapse following transplantation in haematological malignancies and improved outcomes in solid tumours, but the mechanism remains obscure. Therefore we investigated how KIR2DS2 expression impacts NK cell function. Using a novel flow cytometry panel, we show that human NK cells with high KIR2DS2 expression have enhanced spontaneous activation against malignant B cell lines, liver cancer cell lines and primary chronic lymphocytic leukaemia (CLL) cells. Surface expression of CD16 was increased on KIR2DS2high NK cells and accordingly, KIR2DS2high NK cells had increased activation against lymphoma cells coated with the clinically relevant anti-CD20 antibodies rituximab and obinutuzumab. Bulk RNA sequencing revealed that KIR2DS2high NK cells have upregulation of NK mediated cytotoxicity, translation and FCGR gene pathways. We developed a novel single-cell RNA sequencing technique to identify KIR2DS2+ NK cells and this confirmed that KIR2DS2 is associated with enhanced NK cell mediated cytotoxicity. This study provides evidence that KIR2DS2 marks a population of NK cells primed for anti-cancer activity and indicates that KIR2DS2 is an attractive target for NK based therapeutic strategies.
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影响因子：
3.7
作者：
Beksac K;Beksac M;Dalva K;Karaagaoglu E;Tirnaksiz MB
通讯作者：
Tirnaksiz MB
DOI：
10.1073/pnas.1322052111
发表时间：
2014-02-18
影响因子：
11.1
作者：
Liu, Jingxian;Xiao, Ziwei;Ren, Ee Chee
通讯作者：
Ren, Ee Chee
影响因子：
20.3
作者：
Kohrt, Holbrook E.;Thielens, Ariane;Andre, Pascale
通讯作者：
Andre, Pascale
影响因子：
20.3
作者：
Almalte, Zaema;Samarani, Suzanne;Ahmad, Ali
通讯作者：
Ahmad, Ali
影响因子：
4.7
作者：
Fisher JG;Walker CJ;Doyle AD;Johnson PW;Forconi F;Cragg MS;Landesman Y;Khakoo SI;Blunt MD
通讯作者：
Blunt MD