Identification of prostate-specific G-protein coupled receptor as a tumor antigen recognized by CD8(+) T cells for cancer immunotherapy.
Identification of prostate-specific G-protein coupled receptor as a tumor antigen recognized by CD8(+) T cells for cancer immunotherapy.
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DOI：
10.1371/journal.pone.0045756
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang HY
中科院分区：
文献类型：
--
作者：
Matsueda S;Wang M;Weng J;Li Y;Yin B;Zou J;Li Q;Zhao W;Peng W;Legras X;Loo C;Wang RF;Wang HY
前列腺癌是美国老年男性中最常见的癌症，免疫疗法已被证明是治疗转移性去势抵抗性前列腺癌患者的一种有前途的策略。鉴定新的前列腺特异性肿瘤抗原的努力将促进针对前列腺癌的有效癌症疫苗的开发。前列腺特异性G蛋白偶联受体（PSGR）是一种新的抗原，已被证明在人前列腺癌组织中特异性过表达。在这项研究中，我们描述了识别PSGR衍生的肽表位识别的CD 8 + T细胞在HLA-A2依赖的方式。基于HLA-A2结合基序的免疫信息学方法预测了21个PSGR衍生肽。检查这些肽在从HLA-A2+健康供体或HLA-A2+前列腺癌患者获得的外周血单核细胞（PBMC）中诱导肽特异性T细胞应答的能力。还测试了HLA-A2阳性和表达PSGR的LNCaP细胞的识别。在21种PSGR衍生的肽中，三种肽PSGR 3、PSGR 4和PSGR 14经常在来自健康供体和前列腺癌患者的PBMC中诱导肽特异性T细胞应答。重要的是，这些肽特异性T细胞以HLA I类限制性方式识别并杀死LNCaP前列腺癌细胞。我们已经鉴定了三种新的HLA-A2限制性PSGR衍生肽，其被CD 8 + T细胞识别，进而识别HLA-A2+和PSGR+肿瘤细胞。所鉴定的PSGR衍生肽可用作诊断标记物以及用于开发抗癌疫苗的免疫靶标。
Prostate cancer is the most common cancer among elderly men in the US, and immunotherapy has been shown to be a promising strategy to treat patients with metastatic castration-resistant prostate cancer. Efforts to identify novel prostate specific tumor antigens will facilitate the development of effective cancer vaccines against prostate cancer. Prostate-specific G-protein coupled receptor (PSGR) is a novel antigen that has been shown to be specifically over-expressed in human prostate cancer tissues. In this study, we describe the identification of PSGR-derived peptide epitopes recognized by CD8+ T cells in an HLA-A2 dependent manner. Twenty-one PSGR-derived peptides were predicted by an immuno-informatics approach based on the HLA-A2 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs) obtained from either HLA-A2+ healthy donors or HLA-A2+ prostate cancer patients. The recognition of HLA-A2 positive and PSGR expressing LNCaP cells was also tested. Among the 21 PSGR-derived peptides, three peptides, PSGR3, PSGR4 and PSGR14 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and prostate cancer patients. Importantly, these peptide-specific T cells recognized and killed LNCaP prostate cancer cells in an HLA class I-restricted manner. We have identified three novel HLA-A2-restricted PSGR-derived peptides recognized by CD8+ T cells, which, in turn, recognize HLA-A2+ and PSGR+ tumor cells. The PSGR-derived peptides identified may be used as diagnostic markers as well as immune targets for development of anticancer vaccines.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
DOI：
10.1038/nrclinonc.2011.116
发表时间：
2011-08-02
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
3.9
作者：
Dudley, ME;Wunderlich, JR;Rosenberg, SA
通讯作者：
Rosenberg, SA
影响因子：
8
作者：
Gu, Z;Thomas, G;Reiter, RE
通讯作者：
Reiter, RE
影响因子：
4.6
作者：
Hammond, AS;Klein, MR;Brookes, RH
通讯作者：
Brookes, RH