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

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 r...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562561/
https://www.ncbi.nlm.nih.gov/pubmed/31096717
http://dx.doi.org/10.3390/cancers11050677
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author 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
author_facet 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
author_sort Conley, Anthony P.
collection PubMed
description 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.
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spelling pubmed-65625612019-06-17 MAGE-A3 Is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma 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 Cancers (Basel) Article 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. MDPI 2019-05-15 /pmc/articles/PMC6562561/ /pubmed/31096717 http://dx.doi.org/10.3390/cancers11050677 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
MAGE-A3 Is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma
title MAGE-A3 Is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma
title_full MAGE-A3 Is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma
title_fullStr MAGE-A3 Is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma
title_full_unstemmed MAGE-A3 Is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma
title_short MAGE-A3 Is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma
title_sort mage-a3 is a clinically relevant target in undifferentiated pleomorphic sarcoma/myxofibrosarcoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562561/
https://www.ncbi.nlm.nih.gov/pubmed/31096717
http://dx.doi.org/10.3390/cancers11050677
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