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MAGE-A3 is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma

1
Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
2
Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
3
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
4
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
5
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
6
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(5), 677; https://doi.org/10.3390/cancers11050677
Received: 4 April 2019 / Revised: 8 May 2019 / Accepted: 10 May 2019 / Published: 15 May 2019
(This article belongs to the Special Issue Application of Next-Generation Sequencing in Cancers)
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Abstract

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.
Keywords: MAGEA3; MAGE family member A3; cancer testis antigen; immunotherapy; adoptive T cell therapy; sarcoma; pleomorphic sarcoma; undifferentiated pleomorphic sarcoma; myxofibrosarcoma; malignant fibrous histiocytoma; tissue microarray MAGEA3; MAGE family member A3; cancer testis antigen; immunotherapy; adoptive T cell therapy; sarcoma; pleomorphic sarcoma; undifferentiated pleomorphic sarcoma; myxofibrosarcoma; malignant fibrous histiocytoma; tissue microarray
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Conley, A.P.; Wang, W.-L.; Livingston, J.A.; Ravi, V.; Tsai, J.-W.; Ali, A.; Ingram, D.R.; Lowery, C.D.; Roland, C.L.; Somaiah, N.; Hwu, P.; Yee, C.; Subbiah, V.; Futreal, A.; Lazar, A.J.; Patel, S.; Roszik, J. MAGE-A3 is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma. Cancers 2019, 11, 677.

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