Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma
Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma
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DOI：
10.1158/2326-6066.cir-13-0113
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发表时间：
2013-11-01
影响因子：
10.1
通讯作者：
van den Broek, Maries
中科院分区：
文献类型：
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作者：
Dannenmann, Stefanie R.;Hermanns, Thomas;van den Broek, Maries
肾细胞癌（RCC）是一种异质性肾癌，以透明细胞癌（ccRCC）为主要亚组。为了扩大免疫治疗可靶向的临床相关肿瘤相关抗原（TAA）的数量，我们分析了23例原发性ccRCC患者样本中各种TAA的表达和免疫原性。我们发现MAGE-A9和NY-ESO-1分别在36%和55%的样本中高频表达，PRAME、RAGE-1、CA-IX、Cyclin D1、ADFP、C-MET和RGS-5在许多肿瘤样本中过表达。我们分析了HLA-A2(+) ccRCC患者的血液中是否存在taa衍生的HLA-A2限制性肽特异性CD8(+) T细胞，发现6例cyclin D1阳性肿瘤患者中有5例对cyclin D1有自发反应。Cyclin d1特异性CD8(+) T细胞分泌tnf - α、ifn - γ和白细胞介素-2 (IL-2)，并脱颗粒，表明这些ccRCC患者血液中存在多功能肿瘤特异性CD8(+) T细胞。在83%的ccRCC患者中，Cyclin D1的高频率（43%）过表达和功能性Cyclin D1特异性T细胞的存在表明，Cyclin D1可能是免疫治疗策略的靶点。(c) 2013年aacr。
Renal cell carcinoma (RCC) is a heterogeneous group of kidney cancers with clear cell RCC(ccRCC) as the major subgroup. To expand the number of clinically relevant tumor-associated antigens (TAA) that can be targeted by immunotherapy, we analyzed samples from 23 patients with primary ccRCC for the expression and immunogenicity of various TAAs. We found high-frequency expression of MAGE-A9 and NY-ESO-1 in 36% and 55% of samples, respectively, and overexpression of PRAME, RAGE-1, CA-IX, Cyclin D1, ADFP, C-MET, and RGS-5 in many of the tumor samples. We analyzed the blood of patients with HLA-A2(+) ccRCC for the presence of CD8(+) T cells specific for TAA-derived HLA-A2-restricted peptides and found spontaneous responses to cyclin D1 in 5 of 6 patients with Cyclin D1-positive tumors. Cyclin D1-specific CD8(+) T cells secreted TNF-alpha, IFN-gamma, and interleukin-2 (IL-2), and degranulated, indicating the presence of polyfunctional tumor-specific CD8(+) T cells in the blood of these patients with ccRCC. The high frequency (43%) of Cyclin D1 overexpression and the presence of functional cyclin D1-specific T cells in 83% of these patients with ccRCC suggest that cyclin D1 may be a target for immunotherapeutic strategies. (C) 2013 AACR.