Ayyoub Maha, Merlo Andrea, Hesdorffer Charles S, Rimoldi Donata, Speiser Daniel, Cerottini Jean-Charles, Chen Yao-Tseng, Old Lloyd J, Stevanovic Stefan, Valmori Danila
Ludwig Institute Clinical Trial Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
J Immunol. 2005 Apr 15;174(8):5092-9. doi: 10.4049/jimmunol.174.8.5092.
Genes of the synovial sarcoma X breakpoint (SSX) family are expressed in different human tumors, including melanomas, but not in adult somatic tissues. Because of their specific expression at the tumor site, SSX-encoded Ags are potential targets for anticancer immunotherapy. In this study, we have analyzed CD4+ T cell responses directed against the Ag encoded by SSX-4. Upon in vitro stimulation of PBMC from four melanoma patients bearing Ag-expressing tumors with a pool of long peptides spanning the protein sequence, we detected and isolated SSX-4-specific CD4+ T cells recognizing several distinct antigenic sequences, mostly restricted by frequently expressed HLA class II alleles. The majority of the identified sequences were located within the Krüppel-associated box domain in the N-terminal region of the protein, indicating a high potential immunogenicity of this region. Together our data document the existence of CD4+ T cells specific for multiple SSX-4 derived sequences in circulating lymphocytes from melanoma patients and encourage further studies to assess the impact of SSX-4-specific T cell responses on disease evolution in cancer patients.
滑膜肉瘤X断点（SSX）家族的基因在包括黑色素瘤在内的不同人类肿瘤中表达，但在成人体细胞组织中不表达。由于它们在肿瘤部位的特异性表达，SSX编码的抗原是抗癌免疫治疗的潜在靶点。在本研究中，我们分析了针对SSX - 4编码抗原的CD4 + T细胞反应。在用跨越蛋白质序列的一组长肽体外刺激来自四名携带表达抗原肿瘤的黑色素瘤患者的外周血单核细胞（PBMC）后，我们检测并分离出了识别几种不同抗原序列的SSX - 4特异性CD4 + T细胞，这些序列大多受频繁表达的HLA II类等位基因限制。大多数已鉴定的序列位于蛋白质N端区域的Krüppel相关盒结构域内，表明该区域具有高度潜在免疫原性。我们的数据共同证明了黑色素瘤患者循环淋巴细胞中存在针对多个SSX - 4衍生序列的CD4 + T细胞，并鼓励进一步研究以评估SSX - 4特异性T细胞反应对癌症患者疾病进展的影响。
