A polymorphism in the splice donor site of ZNF419 results in the novel renal cell carcinoma-associated minor histocompatibility antigen ZAPHIR.
A polymorphism in the splice donor site of ZNF419 results in the novel renal cell carcinoma-associated minor histocompatibility antigen ZAPHIR.
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DOI：
10.1371/journal.pone.0021699
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Dolstra H
中科院分区：
文献类型：
--
作者：
Broen K;Levenga H;Vos J;van Bergen K;Fredrix H;Greupink-Draaisma A;Kester M;Falkenburg JH;de Mulder P;de Witte T;Griffioen M;Dolstra H
非清髓性异基因造血干细胞移植（SCT）可诱导肾细胞癌（RCC）患者缓解，但这种移植物抗肿瘤（GVT）效应常伴有移植物抗宿主病（GVHD）。在这里，我们评估了2例转移性肾细胞癌患者的次要组织相容性抗原（MiHA）特异性T细胞反应，这些患者接受了降低强度的预处理SCT，然后接受供体淋巴细胞输注（DLI）。1例患者病情稳定并出现SMCY，DLI后观察到A2特异性CD8 + T细胞，具有靶向表达SMCY的RCC肿瘤细胞的潜力。第二名患者经历了肺转移的部分消退，我们从其分离出具有靶向RCC细胞系的能力的MiHA特异性CTL克隆。全基因组关联扫描显示，该CTL识别一种新的HLA-B7限制性MiHA，命名为ZAPHIR，由ZNF 419基因剪接供体位点的多态性引起。四聚体分析显示，外周血中ZAPHIR特异性CD8 + T细胞的出现发生在GVHD不存在的情况下。此外，ZAPHIR在实体瘤细胞系中的表达表明ZAPHIR特异性CD8 + T细胞应答参与选择性GVT免疫。这些发现表明，ZNF 419编码的MiHA ZAPHIR是同种异体SCT后特异性免疫治疗的有吸引力的靶标。
Nonmyeloablative allogeneic stem cell transplantation (SCT) can induce remission in patients with renal cell carcinoma (RCC), but this graft-versus-tumor (GVT) effect is often accompanied by graft-versus-host disease (GVHD). Here, we evaluated minor histocompatibility antigen (MiHA)-specific T cell responses in two patients with metastatic RCC who were treated with reduced-intensity conditioning SCT followed by donor lymphocyte infusion (DLI). One patient had stable disease and emergence of SMCY.A2-specific CD8+ T cells was observed after DLI with the potential of targeting SMCY-expressing RCC tumor cells. The second patient experienced partial regression of lung metastases from whom we isolated a MiHA-specific CTL clone with the capability of targeting RCC cell lines. Whole genome association scanning revealed that this CTL recognizes a novel HLA-B7-restricted MiHA, designated ZAPHIR, resulting from a polymorphism in the splice donor site of the ZNF419 gene. Tetramer analysis showed that emergence of ZAPHIR-specific CD8+ T cells in peripheral blood occurred in the absence of GVHD. Furthermore, the expression of ZAPHIR in solid tumor cell lines indicates the involvement of ZAPHIR-specific CD8+ T cell responses in selective GVT immunity. These findings illustrate that the ZNF419-encoded MiHA ZAPHIR is an attractive target for specific immunotherapy after allogeneic SCT.
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影响因子：
20.3
作者：
Jedema, I;van der Werff, NM;Falkenburg, JHF
通讯作者：
Falkenburg, JHF
影响因子：
11.5
作者：
Tykodi, SS;Warren, EH;Sandmaier, BM
通讯作者：
Sandmaier, BM
影响因子：
15.9
作者：
Takahashi, Yoshiyuki;Harashima, Nanae;Childs, Richard W.
通讯作者：
Childs, Richard W.
影响因子：
6.2
作者：
Pedrazzoli, P;Da Prada, GA;Della Cuna, GR
通讯作者：
Della Cuna, GR
DOI：
10.1084/jem.189.2.301
发表时间：
1999-01-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dolstra H;Fredrix H;Maas F;Coulie PG;Brasseur F;Mensink E;Adema GJ;de Witte TM;Figdor CG;van de Wiel-van Kemenade E
通讯作者：
van de Wiel-van Kemenade E