Naturally acquired MAGE-A10- and SSX-2-specific CD8+ T cell responses in patients with hepatocellular carcinoma
Naturally acquired MAGE-A10- and SSX-2-specific CD8+ T cell responses in patients with hepatocellular carcinoma
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DOI：
10.4049/jimmunol.174.3.1709
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发表时间：
2005-02-01
影响因子：
4.4
通讯作者：
Speiser, DE
中科院分区：
文献类型：
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作者：
Bricard, G;Bouzourene, H;Speiser, DE
免疫疗法被提议用于治疗肝细胞癌（HCC）患者。然而，需要对肿瘤抗原表达和特异性免疫细胞的更详细的知识来制备高度靶向的疫苗。肝癌表达多种肿瘤特异性抗原，这就提出了一个问题，即肝癌患者体内是否存在特异性针对这些抗原的CTL。事实上，最近的一项研究揭示了在HCC患者的肿瘤浸润淋巴细胞中对两种癌症-睾丸（CT）Ag（MAGE-A1和MAGE-A3）具有特异性的CTL。在这里，我们评估了对其他CT Ag：MAGE-A10、SSX-2、NY-ESO-1和拉格-1具有特异性的T细胞的存在，如在HLA-A2（+）黑素瘤患者中所证明的，这些CT Ag是天然免疫原性的。在6名HLA-A2（+）HCC患者中，我们发现2名患者的MAGE-A10和/或SSX-2特异性CD 8（+）T细胞对疾病有天然反应，因为它们在肿瘤病变中富集，而不是在非肿瘤肝脏中。分离的T细胞在体外特异性和强烈地杀伤肿瘤细胞，提供了这些CTL在体内被选择用于高亲和力Ag识别的证据。因此。除了黑素瘤HCC是第二种具有T细胞体内肿瘤识别的明确证据的人实体肿瘤，基于用CT Ag如MAGE-A10和SSX-2免疫，为特异性免疫治疗提供了依据。
Immunotherapy is being proposed to treat patients with hepatocellular carcinoma (HCC). However, more detailed knowledge on tumor Ag expression and specific immune cells is required for the preparation of highly targeted vaccines. HCC express a variety of tumor-specific Ags, raising the question whether CTL specific for such Ags exist in HCC patients. Indeed, a recent study revealed CTLs specific for two cancer-testis (CT) Ags (MAGE-A1 and MAGE-A3) in tumor infiltrating lymphocytes of HCC patients. Here we assessed the presence of T cells specific for additional CT Ags: MAGE-A10, SSX-2, NY-ESO-1, and LAGE-1, which are naturally immunogenic as demonstrated in HLA-A2(+) melanoma patients. In two of six HLA-A2(+) HCC patients, we found that MAGE-A10- and/or SSX-2-specific CD8(+) T cells naturally responded to the disease, because they were enriched in tumor lesions but not in nontumoral liver. Isolated T cells specifically and strongly killed tumor cells in vitro, providing evidence that these CTL were selected in vivo for high avidity Ag recognition. Therefore. besides melanoma. HCC is the second solid human tumor with clear evidence for in vivo tumor recognition by T cells, providing the rational for specific immunotherapy, based on immunization with CT Ags such as MAGE-A10 and SSX-2.