MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia.
MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia.
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DOI：
10.1126/scitranslmed.3006061
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发表时间：
2013-09-18
影响因子：
17.1
通讯作者：
Engelhard VH
中科院分区：
文献类型：
--
作者：
Cobbold M;De La Peña H;Norris A;Polefrone JM;Qian J;English AM;Cummings KL;Penny S;Turner JE;Cottine J;Abelin JG;Malaker SA;Zarling AL;Huang HW;Goodyear O;Freeman SD;Shabanowitz J;Pratt G;Craddock C;Williams ME;Hunt DF;Engelhard VH
涉及磷酸化的信号通路的解除管制是恶性转化的标志。磷酸化蛋白的降解产生与MHC-I和II分子相关的癌症特异性磷酸肽，并被t细胞识别。我们在原发性血液学肿瘤和正常组织表面发现了95个磷酸肽，其中61个是肿瘤特异性的。磷酸肽在更具侵袭性和恶性的样本中更为普遍。这些磷酸化肽特异性的CD8 t细胞系在体外识别并杀死白血病细胞系和hla匹配的原发性白血病细胞。健康个体对循环记忆区中许多磷酸肽表现出惊人的高水平CD8 t细胞反应。这种免疫在一些白血病患者中显著降低或缺失，这与临床结果相关，并在同种异体干细胞移植后恢复。这些结果表明，磷酸肽可能是人类癌症免疫监测的靶点，并指出它们对基于疫苗和t细胞过继转移免疫疗法的发展的重要性。
Deregulation of signaling pathways involving phosphorylation is a hallmark of malignant transformation. Degradation of phosphoproteins generates cancer-specific phosphopeptides that are associated with MHC-I and II molecules and recognized by T-cells. We identified 95 phosphopeptides presented on the surface of primary hematological tumors and normal tissues, including 61 that were tumor-specific. Phosphopeptides were more prevalent on more aggressive and malignant samples. CD8 T-cell lines specific for these phosphopeptides recognized and killed both leukemia cell lines and HLA-matched primary leukemia cells ex vivo. Healthy individuals showed surprisingly high levels of CD8 T-cell responses against many of these phosphopeptides within the circulating memory compartment. This immunity was significantly reduced or absent in some leukemia patients, which correlated with clinical outcome, and was restored following allogeneic stem cell transplantation. These results suggest that phosphopeptides may be targets of cancer immune surveillance in humans, and point to their importance for development of vaccine-based and T-cell adoptive transfer immunotherapies..
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DOI：
10.1073/pnas.96.15.8639
发表时间：
1999-07-20
影响因子：
11.1
作者：
Bonnett, D;Warren, EH;Riddell, SR
通讯作者：
Riddell, SR
影响因子：
4.8
作者：
Kröger, N;Brand, R;de Witte, T
通讯作者：
de Witte, T
影响因子：
15.3
作者：
Arentz-Hansen, H;Korner, R;Molberg, O;Quarsten, H;Vader, W;Kooy, Y M;Lundin, K E;Koning, F;Roepstorff, P;Sollid, L M;McAdam, S N
通讯作者：
McAdam, S N
DOI：
10.1186/1745-7580-3-3
发表时间：
2007-02-21
期刊：
Immunome research
影响因子：
--
作者：
Beaver JE;Bourne PE;Ponomarenko JV
通讯作者：
Ponomarenko JV
影响因子：
158.5
作者：
Druker, Brian J.;Guilhot, Francois;Larson, Richard A.
通讯作者：
Larson, Richard A.