| Autor: |
Luk SJ; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., van der Steen DM; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Hagedoorn RS; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Jordanova ES; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.; Center for Gynecological Oncology Amsterdam, Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands., Schilham MW; Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands., Bovée JV; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands., Cleven AH; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands., Falkenburg JF; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Szuhai K; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands., Heemskerk MH; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands. |
| Abstrakt: |
Synovial sarcoma expresses multiple cancer testis antigens that could potentially be targeted by T-cell receptor (TCR) gene therapy. In this study we investigated whether PRAME-TCR-gene therapy could be an effective treatment for synovial sarcoma by investigating the potential of PRAME-specific T-cells to recognize sarcoma cells and by evaluating the expression patterns of PRAME and HLA class I (HLA-I) in synovial sarcoma tumor samples. All PRAME expressing sarcoma cell lines, including 2 primary synovial sarcoma cell cultures (passage < 3), were efficiently recognized by PRAME-specific T-cells. mRNA FISH demonstrated that PRAME was expressed in all synovial sarcoma samples, mostly in an homogeneous pattern. Immunohistochemistry demonstrated low HLA-I baseline expression in synovial sarcoma, but its expression was elevated in specific areas of the tumors, especially in biphasic components of biphasic synovial sarcoma. In 5/11 biphasic synovial sarcoma patients and in 1/17 monophasic synovial sarcoma patients, elevated HLA-I on tumor cells was correlated with infiltration of T-cells in these specific areas. In conclusion, low-baseline expression of HLA-I in synovial sarcoma is elevated in biphasic areas and in areas with densely infiltrating T-cells, which, in combination with homogeneous and high PRAME expression, makes synovial sarcoma potentially a suitable candidate for PRAME-specific TCR-gene therapy. |
