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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6562561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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