Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Invest Ophthalmol Vis Sci. 2023 Dec 1;64(15):36. doi: 10.1167/iovs.64.15.36.
Uveal melanoma (UM) is a rare disease with a high mortality, and new therapeutic options are being investigated. Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer testis antigen, expressed in the testis, but also in cancers, including uveal melanoma. PRAME is considered a target for immune therapy in several cancers, and PRAME-specific T cell clones have been shown to kill UM cells.
We studied the literature on PRAME expression in hematological and solid malignancies, including UM, and its role as a target for immunotherapy. The distribution of tumor features was compared between PRAME-high and PRAME-low UM in a 64-patient cohort from the Leiden University Medical Center (LUMC) and in the Cancer Genome Atlas (TCGA) cohort of 80 cases and differential gene expression analysis was performed in the LUMC cohort.
PRAME is expressed in many malignancies, it is frequently associated with a negative prognosis, and can be the target of T cell receptor (TCR)-transduced T cells, a promising treatment option with high avidity and safety. In UM, PRAME is expressed in 26% to 45% of cases and is correlated with a worse prognosis. In the LUMC and the TCGA cohorts, high PRAME expression was associated with larger diameter, higher Tumor-Node-Metastasis (TNM) stage, more frequent gain of chromosome 8q, and an inflammatory phenotype.
We confirm that PRAME is associated with poor prognosis in UM and has a strong connection with extra copies of 8q. We show that PRAME-specific immunotherapy in an adjuvant setting is promising in treatment of malignancies, including UM.
葡萄膜黑色素瘤（UM）是一种死亡率很高的罕见疾病，目前正在研究新的治疗方法。优先表达的黑色素瘤抗原（PRAME）是一种癌症睾丸抗原，在睾丸中表达，但也在包括葡萄膜黑色素瘤在内的癌症中表达。PRAME 被认为是几种癌症免疫治疗的靶点，并且已经证明 PRAME 特异性 T 细胞克隆能够杀死 UM 细胞。
我们研究了 PRAME 在血液系统恶性肿瘤和实体恶性肿瘤中的表达及其作为免疫治疗靶点的作用，包括 UM。我们比较了来自莱顿大学医学中心（LUMC）的 64 例患者队列和癌症基因组图谱（TCGA）的 80 例队列中 PRAME 高表达和 PRAME 低表达的 UM 患者的肿瘤特征分布，并对 LUMC 队列进行了差异基因表达分析。
PRAME 在许多恶性肿瘤中表达，它通常与不良预后相关，并且可以成为 T 细胞受体（TCR）转导的 T 细胞的靶点，这是一种具有高亲和力和安全性的很有前途的治疗选择。在 UM 中，PRAME 在 26%至 45%的病例中表达，与预后较差相关。在 LUMC 和 TCGA 队列中，高 PRAME 表达与更大的直径、更高的肿瘤-淋巴结-转移（TNM）分期、8q 染色体增益的频率更高以及炎症表型相关。
我们证实 PRAME 与 UM 的不良预后相关，并且与 8q 染色体的额外拷贝有很强的联系。我们表明，在辅助治疗中使用 PRAME 特异性免疫疗法治疗包括 UM 在内的恶性肿瘤具有广阔的前景。
