Heparanase:: A new metastasis-associated antigen recognized in breast cancer patients by spontaneously induced memory T lymphocytes
Heparanase:: A new metastasis-associated antigen recognized in breast cancer patients by spontaneously induced memory T lymphocytes
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DOI：
10.1158/0008-5472.can-05-2363
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发表时间：
2006-08-01
期刊：
影响因子：
11.2
通讯作者：
Schirrmacher, Volker
中科院分区：
文献类型：
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作者：
Sommerfeldt, Nora;Beckhove, Philipp;Schirrmacher, Volker
乙酰肝素酶（Hpa）的表达和分泌增加的肿瘤细胞通过细胞外基质，组织破坏，血管生成和转移促进肿瘤侵袭。在这里，我们显示存在于乳腺癌患者的Hpa特异性T淋巴细胞的荧光激活细胞分选流式细胞术使用Hpa肽-MHC I类四聚体。此外，我们还显示了高比例的乳腺癌患者对Hpa衍生的HLA-A2限制性肽的记忆性T细胞应答，导致IFN-γ的产生和裂解乳腺癌细胞的抗肿瘤CTL的产生。这样的CTL识别在Hpa转染的和表达Hpa的未转染的乳腺癌细胞上内源性加工的相应Hpa肽。根据这些结果以及在健康人中未发现此类细胞的事实，Hpa似乎是一种有吸引力的新的肿瘤相关抗原，其HLA-A2限制性肽应该是肽疫苗接种以重新激活对侵袭性和转移性癌细胞的记忆免疫应答的良好候选物。
Increased expression and secretion of heparanase (Hpa) by tumor cells promotes tumor invasion through extracellular matrices, tissue destruction, angiogenesis, and metastasis. Here, we show the existence in breast cancer patients of Hpa-specific T lymphocytes by fluorescence-activated cell sorting flow cytometry using Hpa peptide-MHC class I tetramers. We furthermore show memory T-cell responses in a high proportion of breast cancer patients to Hpa-derived HLA-A2-restricted peptides, leading to production of IFN-gamma and to generation of antitumor CTLs lysing breast cancer cells. Such CTLs recognized endogenously processed respective Hpa peptides on Hpa-transfected and Hpa-expressing untransfected breast carcinoma cells. According to these results and to the fact that such cells were not found in healthy people, Hpa seems to be an attractive new tumor-associated antigen and its HLA-A2-restricted peptides ought to be good candidates for peptide vaccination to reactivate memory immune responses to invasive and metastatic cancer cells.