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MYCN: from oncoprotein to tumor-associated antigen
MYCN is a well-known oncogene over-expressed in different human malignancies including neuroblastoma (NB), rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms’ tumor, and small cell lung cancer. In the case of NB, MYCN amplification is an established biomarker of poor-prognosis. MYCN belongs to a...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499703/ https://www.ncbi.nlm.nih.gov/pubmed/23162796 http://dx.doi.org/10.3389/fonc.2012.00174 |
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author | Pistoia, Vito Morandi, Fabio Pezzolo, Annalisa Raffaghello, Lizzia Prigione, Ignazia |
author_facet | Pistoia, Vito Morandi, Fabio Pezzolo, Annalisa Raffaghello, Lizzia Prigione, Ignazia |
author_sort | Pistoia, Vito |
collection | PubMed |
description | MYCN is a well-known oncogene over-expressed in different human malignancies including neuroblastoma (NB), rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms’ tumor, and small cell lung cancer. In the case of NB, MYCN amplification is an established biomarker of poor-prognosis. MYCN belongs to a family of transcription factors (the most important of which is C-MYC) that show a high degree of homology. Down-regulation of MYC protein expression leads to tumor regression in animal models, indicating that MYC proteins represent interesting therapeutic targets. Pre-requisites for a candidate tumor-associated antigen (TAA) to be targeted by immunotherapeutic approaches are the following, (i) expression should be tumor-restricted, (ii) the putative TAA should be up-regulated in cancer cells, and (iii) protein should be processed into immunogenic peptides capable of associating to major histocompatibility complex molecules with high affinity. Indeed, the MYCN protein is not expressed in human adult tissues and up-regulated variably in NB cells, and MYCN peptides capable of associating to HLA-A1 or HLA-A2 molecules with high affinity have been identified. Thus the MYCN protein qualifies as putative TAA in NB. Additional issues that determine the feasibility of targeting a putative TAA with cytotoxic T lymphocytes (CTLs) and will be here discussed are the following, (i) the inadequacy of tumor cells per se to act as antigen-presenting cells witnessed, in the case of NB cells, by the low to absent expression of HLA class I molecules, the lack of co-stimulatory molecules and multiple defects in the HLA class I related antigen processing machinery, and (ii) the immune evasion mechanisms operated by cancer cells to fool the host immune system, such as up-regulation of soluble immunosuppressive molecules (e.g., soluble MICA and HLA-G in the case of NB) or generation of immunosuppressive cells in the tumor microenvironment. A final issue that deserves consideration is the strategy used to generate CTL. |
format | Online Article Text |
id | pubmed-3499703 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-34997032012-11-16 MYCN: from oncoprotein to tumor-associated antigen Pistoia, Vito Morandi, Fabio Pezzolo, Annalisa Raffaghello, Lizzia Prigione, Ignazia Front Oncol Oncology MYCN is a well-known oncogene over-expressed in different human malignancies including neuroblastoma (NB), rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms’ tumor, and small cell lung cancer. In the case of NB, MYCN amplification is an established biomarker of poor-prognosis. MYCN belongs to a family of transcription factors (the most important of which is C-MYC) that show a high degree of homology. Down-regulation of MYC protein expression leads to tumor regression in animal models, indicating that MYC proteins represent interesting therapeutic targets. Pre-requisites for a candidate tumor-associated antigen (TAA) to be targeted by immunotherapeutic approaches are the following, (i) expression should be tumor-restricted, (ii) the putative TAA should be up-regulated in cancer cells, and (iii) protein should be processed into immunogenic peptides capable of associating to major histocompatibility complex molecules with high affinity. Indeed, the MYCN protein is not expressed in human adult tissues and up-regulated variably in NB cells, and MYCN peptides capable of associating to HLA-A1 or HLA-A2 molecules with high affinity have been identified. Thus the MYCN protein qualifies as putative TAA in NB. Additional issues that determine the feasibility of targeting a putative TAA with cytotoxic T lymphocytes (CTLs) and will be here discussed are the following, (i) the inadequacy of tumor cells per se to act as antigen-presenting cells witnessed, in the case of NB cells, by the low to absent expression of HLA class I molecules, the lack of co-stimulatory molecules and multiple defects in the HLA class I related antigen processing machinery, and (ii) the immune evasion mechanisms operated by cancer cells to fool the host immune system, such as up-regulation of soluble immunosuppressive molecules (e.g., soluble MICA and HLA-G in the case of NB) or generation of immunosuppressive cells in the tumor microenvironment. A final issue that deserves consideration is the strategy used to generate CTL. Frontiers Media S.A. 2012-11-16 /pmc/articles/PMC3499703/ /pubmed/23162796 http://dx.doi.org/10.3389/fonc.2012.00174 Text en Copyright © Pistoia, Morandi, Pezzolo, Raffaghello and Prigione. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. |
spellingShingle | Oncology Pistoia, Vito Morandi, Fabio Pezzolo, Annalisa Raffaghello, Lizzia Prigione, Ignazia MYCN: from oncoprotein to tumor-associated antigen |
title | MYCN: from oncoprotein to tumor-associated antigen |
title_full | MYCN: from oncoprotein to tumor-associated antigen |
title_fullStr | MYCN: from oncoprotein to tumor-associated antigen |
title_full_unstemmed | MYCN: from oncoprotein to tumor-associated antigen |
title_short | MYCN: from oncoprotein to tumor-associated antigen |
title_sort | mycn: from oncoprotein to tumor-associated antigen |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499703/ https://www.ncbi.nlm.nih.gov/pubmed/23162796 http://dx.doi.org/10.3389/fonc.2012.00174 |
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