PMID- 31096717 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 11 IP - 5 DP - 2019 May 15 TI - MAGE-A3 is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma. LID - 10.3390/cancers11050677 [doi] LID - 677 AB - 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. FAU - Conley, Anthony P AU - Conley AP AD - Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. aconley@mdanderson.org. FAU - Wang, Wei-Lien AU - Wang WL AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. wlwang@mdanderson.org. FAU - Livingston, John A AU - Livingston JA AD - Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. JALivingston@mdanderson.org. FAU - Ravi, Vinod AU - Ravi V AD - Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. vravi@mdanderson.org. FAU - Tsai, Jen-Wei AU - Tsai JW AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. jwtsai0317@gmail.com. FAU - Ali, Ali AU - Ali A AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. ali.ali@bcm.edu. FAU - Ingram, Davis R AU - Ingram DR AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. DRIngram@mdanderson.org. FAU - Lowery, Caitlin D AU - Lowery CD AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. caitlin.d.may@gmail.com. FAU - Roland, Christina L AU - Roland CL AD - Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. CLRoland@mdanderson.org. FAU - Somaiah, Neeta AU - Somaiah N AD - Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. NSomaiah@mdanderson.org. FAU - Hwu, Patrick AU - Hwu P AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. phwu@mdanderson.org. FAU - Yee, Cassian AU - Yee C AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. CYee@mdanderson.org. FAU - Subbiah, Vivek AU - Subbiah V AD - Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. VSubbiah@mdanderson.org. FAU - Futreal, Andrew AU - Futreal A AD - Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. AFutreal@mdanderson.org. FAU - Lazar, Alexander J AU - Lazar AJ AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. alazar@mdanderson.org. FAU - Patel, Shreyaskumar AU - Patel S AD - Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. spatel@mdanderson.org. FAU - Roszik, Jason AU - Roszik J AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. jroszik@mdanderson.org. AD - Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. jroszik@mdanderson.org. LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20190515 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC6562561 OTO - NOTNLM OT - MAGE family member A3 OT - MAGEA3 OT - adoptive T cell therapy OT - cancer testis antigen OT - immunotherapy OT - malignant fibrous histiocytoma OT - myxofibrosarcoma OT - pleomorphic sarcoma OT - sarcoma OT - tissue microarray OT - undifferentiated pleomorphic sarcoma COIS- The authors declare no conflict of interest. EDAT- 2019/05/18 06:00 MHDA- 2019/05/18 06:01 PMCR- 2019/05/15 CRDT- 2019/05/18 06:00 PHST- 2019/04/04 00:00 [received] PHST- 2019/05/08 00:00 [revised] PHST- 2019/05/10 00:00 [accepted] PHST- 2019/05/18 06:00 [entrez] PHST- 2019/05/18 06:00 [pubmed] PHST- 2019/05/18 06:01 [medline] PHST- 2019/05/15 00:00 [pmc-release] AID - cancers11050677 [pii] AID - cancers-11-00677 [pii] AID - 10.3390/cancers11050677 [doi] PST - epublish SO - Cancers (Basel). 2019 May 15;11(5):677. doi: 10.3390/cancers11050677.