Zhang Jian Gang, Kruse Carol A, Driggers Lara, Hoa Neil, Wisoff Jeffrey, Allen Jeffrey C, Zagzag David, Newcomb Elizabeth W, Jadus Martin R
Department of Pathology, University of California at Irvine, Irvine, CA, USA.
J Neurooncol. 2008 May;88(1):65-76. doi: 10.1007/s11060-008-9534-4. Epub 2008 Feb 8.
We evaluated and compared tumor antigen precursor protein (TAPP) profiles in adult and pediatric brain tumors of 31 genes related to tumor associated antigens (TAA) for possible use in immunotherapy. Antigens were selected based on their potential to stimulate T cell responses against tumors of neuroectodermal origin.
Thirty-seven brain tumor specimens from 11 adult and 26 pediatric patients were analyzed by quantitative real-time PCR for the relative expression of 31 TAPP mRNAs. The age range of adults (4F:7M) was 27-77 years (median 51.5 +/- 14.5 years) and for pediatrics (12F:14M) was 0.9-19 years (median 8.3 +/- 5.5 years). Histological diagnoses consisted of 16 glioblastomas, 4 low grade astrocytomas, 10 juvenile pilocytic astrocytomas, and 7 ependymomas.
The adult gliomas expressed 94% (29 of 31) of the TAPP mRNAs evaluated compared with pediatric brain tumors that expressed 55-74% of the TAPP mRNAs, dependent on tumor histological subtype. Four types of TAPP expression patterns were observed: (1) equal expression among adult and pediatric cases, (2) greater expression in adult than pediatric cases, (3) expression restricted to adult GBM and (4) a random distribution. The pediatric brain tumors lacked expression of some genes associated with engendering tumor survival, such as hTert and Survivin.
The potential TAA targets identified from the TAPP profiles of 31 genes associated with adult and pediatric brain tumors may help investigators select specific target antigens for developing dendritic cell- or peptide-based vaccines or T cell-based immunotherapeutic approaches against brain tumors.
我们评估并比较了成人和儿童脑肿瘤中与肿瘤相关抗原(TAA)相关的31个基因的肿瘤抗原前体蛋白(TAPP)谱,以探讨其在免疫治疗中的潜在应用。基于抗原刺激针对神经外胚层起源肿瘤的T细胞反应的潜力来选择抗原。
对来自11名成人和26名儿童患者的37份脑肿瘤标本进行定量实时PCR分析,以检测31种TAPP mRNA的相对表达。成人(4名女性:7名男性)年龄范围为27 - 77岁(中位年龄51.5±14.5岁),儿童(12名女性:14名男性)年龄范围为0.9 - 19岁(中位年龄8.3±5.5岁)。组织学诊断包括16例胶质母细胞瘤、4例低级别星形细胞瘤、10例幼年型毛细胞星形细胞瘤和7例室管膜瘤。
与表达55 - 74% TAPP mRNA的儿童脑肿瘤相比,成人胶质瘤表达了所评估的94%(31种中的29种)TAPP mRNA,这取决于肿瘤组织学亚型。观察到四种TAPP表达模式:(1)成人和儿童病例中表达相等;(2)成人中表达高于儿童病例;(3)仅在成人胶质母细胞瘤中表达;(4)随机分布。儿童脑肿瘤缺乏一些与肿瘤存活相关基因的表达,如hTert和Survivin。
从与成人和儿童脑肿瘤相关的31个基因的TAPP谱中鉴定出的潜在TAA靶点,可能有助于研究人员选择特定的靶抗原,以开发基于树突状细胞或肽的疫苗或针对脑肿瘤的基于T细胞的免疫治疗方法。