Conley Anthony P, Wang Wei-Lien, Livingston John A, Ravi Vinod, Tsai Jen-Wei, Ali Ali, Ingram Davis R, Lowery Caitlin D, Roland Christina L, Somaiah Neeta, Hwu Patrick, Yee Cassian, Subbiah Vivek, Futreal Andrew, Lazar Alexander J, Patel Shreyaskumar, Roszik Jason
Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Cancers (Basel). 2019 May 15;11(5):677. doi: 10.3390/cancers11050677.
Melanoma-associated antigen 3 (MAGE-A3) expression is generally restricted to the placenta and germline cells of the testis, but it may also be expressed in sarcoma and other cancers and is associated with poor prognosis. Immunotherapy approaches targeting MAGE-A3 in other cancers have shown mixed results in the clinic, however, use of cancer testis antigens such as MAGE-A3 may have therapeutic value in the treatment of soft tissue sarcomas. Based on the recent success of anti-programmed death-1 (PD-1) therapy in undifferentiated pleomorphic sarcoma, we hypothesize that MAGE-A3-based immunotherapies may also provide benefits in this sarcoma type. We analyzed MAGE-A3 expression of sarcoma subtypes available in the Cancer Genome Atlas and Cancer Cell Line Encyclopedia and show that undifferentiated pleomorphic sarcoma/myxofibrosarcoma (UPS/MFS) expresses this potential target gene. We have identified high protein expression by tissue microarray of 106 UPS cores. We also found that high MAGE-A3 mRNA and protein expression is associated with worse overall survival in UPS/MFS. Furthermore, our results show no human leukocyte antigen (HLA) expression loss and relatively high lymphocyte infiltration by lymphocyte specific protein tyrosine kinase (LCK) marker expression. Based on these results, we propose targeting MAGE-A3 in UPS/MFS by immunotherapy techniques.
黑色素瘤相关抗原3（MAGE - A3）的表达通常局限于胎盘和睾丸的生殖系细胞，但它也可能在肉瘤和其他癌症中表达，并与预后不良相关。针对其他癌症中MAGE - A3的免疫治疗方法在临床上取得了喜忧参半的结果，然而，使用诸如MAGE - A3之类的癌睾丸抗原可能在软组织肉瘤的治疗中具有治疗价值。基于抗程序性死亡-1（PD-1）疗法最近在未分化多形性肉瘤中取得的成功，我们假设基于MAGE - A3的免疫疗法在这种肉瘤类型中也可能带来益处。我们分析了癌症基因组图谱和癌细胞系百科全书中可用的肉瘤亚型的MAGE - A3表达情况，结果显示未分化多形性肉瘤/黏液纤维肉瘤（UPS/MFS）表达了这个潜在的靶基因。我们通过对106个UPS核心组织芯片进行检测，确定了其蛋白高表达。我们还发现，UPS/MFS中MAGE - A3 mRNA和蛋白的高表达与较差的总生存期相关。此外，我们的结果显示没有人类白细胞抗原（HLA）表达缺失，并且通过淋巴细胞特异性蛋白酪氨酸激酶（LCK）标记物表达显示淋巴细胞浸润相对较高。基于这些结果，我们建议通过免疫治疗技术靶向UPS/MFS中的MAGE - A3。
