SSX基因家族研究进展

SSX基因家族由9个成员组成,其中SSX-1、SSX-2和SSX-4经常出现在滑膜肉瘤t(X18)染色体易位的SYT-SSX融合基因中.SSX基因家族可编码肿瘤/睾丸抗原,在睾丸以外的正常组织中,除甲状腺微弱表达外,没有发现它们的存在.HOM-MEL-40是最早用重组cDNA表达文库血清学分析技术确定的由SSX-2基因表达的抗原.近来的研究发现蛋白SSX-241-49是CD8+CTL免疫识别的优势表位,而SSX-237-58和SSX-219-34分别是CD4+T细胞识别相关的HLA-DR及HLA-DP限制表位.日本学者也发现SYT-SSX基因融合蛋白断裂点衍生肽是MHC Ⅰ分子HLA-A24和HLA-B7限制的CTL识别的表位.所有这些研究,证明SSX基因家族编码蛋白是肿瘤免疫治疗有前景的靶标之一.

Progress in SSX gene family

The SSX gene family is composed of 9 members, among which SSX-1, SSX-2, and SSX-4 have been found existing in SYT-SSX fusion gene resulting from the t (X: 18) chromosomal translocation in almost all synovial sarcomas. The gene products encoded by the members of the SSX family belong to the group of the so-called cancer/testis antigens, which were found not to be expressed in normal tissues with exception of testis and the faint expression in thyroid gland. HOM-MEL-40 was originally identified being encoded by the SSX-2 gene in a malignant melanoma using SEREX, the serological analysis of antigens by recombinant expressing cloning. The recent studies have revealed that SSX-S41-49 is an immunodominant CD8+ T cell epitope, while SSX-237_58 is a CD4+ T cell epitope in association with HLA-DR, and SSX-219.34 restricted to HLA-DP. The Japanese scientists have also identified that the peptide derived from the breakpoint of SYT-SSX fusion protein were CTL epitopes restricted to MHC-I molecules of HLA-A24 and HLA-B7 . In conclusion, findings in these studies suggest the SSX proteins are promising targets in cancer immunotherapy.