Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma
Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma
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DOI：
10.1593/neo.04316
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发表时间：
2004-09-01
期刊：
影响因子：
4.8
通讯作者：
Pistoia, V
中科院分区：
文献类型：
--
作者：
Raffaghello, L;Prigione, I;Pistoia, V
神经母细胞瘤（Neuroblastoma， NIB）是一种儿童颅外肿瘤，其特征是人白细胞抗原I类下调和抗原加工机制缺陷，这两个特征使其成为自然杀伤细胞（NK）介导裂解的合适靶点。NKG2D是一种活化免疫受体，由细胞毒性T淋巴细胞和NK细胞表达。NKG2D的配体是主要的组织相容性复合体i类相关链（MIC）A和MICB糖蛋白，以及ul -16结合蛋白（ulbp）。由于缺乏相关信息，本研究在人原发性NB肿瘤和细胞系中研究了NKG2D配体的表达。MICA、MICB和ULBP转录本存在于大多数肿瘤和细胞系中。在一些NB细胞系中检测到MICA蛋白，但在原发肿瘤中未检测到。在大多数患者血清和一些细胞系上清液中发现了可溶性MICA （sMICA）。sMICA下调正常外周血CD8（+）细胞表面NKG2D，降低nk介导的MICA(+) NB细胞杀伤。MICB仅在原发肿瘤和细胞系的细胞质中检测到。大约50%的原发肿瘤表达ULBP-2，但不表达ULBP-1或-3。9株细胞系中有5株表达ULBP-3, 2株表达ULBP-2，而未检测到ULBP-1。这些研究描绘了NB中肿瘤逃逸和免疫缺陷的新的潜在途径。
Neuroblastoma (NIB) is a pediatric extracranial tumor characterized by downregulation of human leukocyte antigen class I and defects of the antigen processing machinery, two features that make it an appropriate target for natural killer (NK)-mediated lysis. NKG2D is an activating immunoreceptor expressed by cytotoxic T lymphocytes and NK cells. The ligands for NKG2D are the major histocompatibility complex class I-related chain (MIC)A and MICB glycoproteins, and the UL-16-binding proteins (ULBPs). Here, the expression of NKG2D ligands was investigated in human primary NB tumors and cell lines because scanty information is available on this issue. MICA, MICB, and ULBP transcripts were found in most tumors and cell lines. MICA protein was detected in some NB cell lines but not in primary tumors. A soluble form of MICA (sMICA) was identified in most patient sera and in some cell line supernatants. sMICA downregulated surface NKG2D in normal peripheral blood CD8(+) cells and decreased NK-mediated killing of MICA(+) NB cells. MICB was detected exclusively in the cytosol of primary tumors and cell lines. Approximately 50% of primary tumors expressed ULBP-2, but not ULBP-1 or -3. ULBP-3 was expressed in 5 of 9 cell lines, ULBP-2 in 2 of 9, whereas ULBP-1 was never detected. These studies delineate novel potential pathways of tumor escape and immunodeficiency in NB.