Detection and Induction of CTLs Specific for SYT-SSX-Derived Peptides in HLA-A24+ Patients with Synovial Sarcoma

• DOI: 10.4049/jimmunol.169.3.1611
• Publication Date: 2014-04-22T04:06:27Z
• Authors: Yuriko Sato; Yuki Nabeta; Tomohide Tsukahara; Yoshihiko Hirohashi; Rong Syunsui; Akiko Maeda; Hiroeki Sahara; Hideyuki Ikeda; Toshihiko Torigoe; Shingo Ichimiya; Takuro Wada; Toshihiko Yamashita; Hiroaki Hiraga; Akira Kawai; Takeshi Ishii; Nobuhito Araki; Akira Myoui; Seiichi Matsumoto; Tohru Umeda; Seiichi Ishii; Satoshi Kawaguchi; Noriyuki Sato
• Keywords: Adult; Male; Adolescent; HLA-A Antigens; Oncogene Proteins, Fusion; Molecular Sequence Data; HLA-A24 Antigen; Middle Aged; Hematopoietic Stem Cells; Translocation, Genetic; Artificial Gene Fusion; 3. Good health; Sarcoma, Synovial; 03 medical and health sciences; 0302 clinical medicine; Tumor Cells, Cultured; Humans; Female; Amino Acid Sequence; Child; Aged; T-Lymphocytes, Cytotoxic

Abstract To investigate the immunogenic property of peptides derived from the synovial sarcoma-specific SYT-SSX fusion gene, we synthesized four peptides according to the binding motif for HLA-A24. The peptides, SS391 (PYGYDQIMPK) and SS393 (GYDQIMPKK), were derived from the breakpoint of SYT-SSX, and SS449a (AWTHRLRER) and SS449b (AWTHRLRERK) were from the SSX region. These peptides were tested for their reactivity with CTL precursors (CTLps) in 16 synovial sarcoma patients using HLA-A24/SYT-SSX peptide tetramers and also for induction of specific CTLs from four HLA-A24+ synovial sarcoma patients. Tetramer analysis indicated that the increased CTLp frequency to the SYT-SSX was associated with pulmonary metastasis in synovial sarcoma patients (p < 0.03). CTLs were induced from PBLs of two synovial sarcoma patients using the peptide mixture of SS391 and SS393, which lysed HLA-A24+ synovial sarcoma cells expressing SYT-SSX as well as the peptide-pulsed target cells in an HLA class I-restricted manner. These findings suggest that aberrantly expressed SYT-SSX gene products have primed SYT-SSX-specific CTLps in vivo and increased their frequency in synovial sarcoma patients. The identification of SYT-SSX peptides may offer an opportunity to design peptide-based immunotherapeutic approaches for HLA-A24+ patients with synovial sarcoma.