PRAME and HLA Class I expression patterns make synovial sarcoma a suitable target for PRAME specific T-cell receptor gene therapy

• Published in: Oncoimmunology Vol. 7; no. 12; p. e1507600
• Main Authors: Luk, Sietse J, Steen, Dirk M van der, Hagedoorn, Renate S, Jordanova, Ekaterina S, Schilham, Marco W, Bovée, Judith VMG, Cleven, Arjen HG, Falkenburg, JH Frederik, Szuhai, Karoly, Heemskerk, Mirjam HM
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02-12-2018; Taylor & Francis Group
• Subjects: HLA Class I; Original Research; PRAME; Synovial sarcoma; T-cell infiltration; TCR-gene therapy; HLA Class I; T-cell infiltration; PRAME; TCR-gene therapy; Synovial sarcoma
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.1080/2162402X.2018.1507600

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.