Abstract
In recent decades our understanding of immune cell activation and homeostasis has significantly expanded. Such progress helped to better define the cellular, molecular, and epigenetic networks involved in the immune response in the tumor microenvironment and renewed the enthusiasm towards the potential power of cancer immunotherapy. However, successful translation of novel mechanistic discoveries into effective immunotherapy was hindered by a number of obstacles, among them the ability of tumors to tolerize host lymphocytes rendering them functionally incompetent and the tumors ability to evade antigen-specific immune recognition through a variety of genetic, epigenetic, and stromal factors. These immunosuppressive strategies have, thus far, blunted our efforts to effectively unleash anti-cancer immunity. Fortunately, the wealth of new information regarding the interactions between tumors and the immune system and the regulation of certain highly antigenic tumor proteins has led to novel approaches with the potential to render cancer cells helpless towards immune attack. Here we summarize recent findings on cancer-induced T-lymphocyte tolerance and discuss a novel “vaccinate-induce” strategy conceived to counteract these effects at an epigenetic level.
Keywords: Histone deacetylase, tolerance, cancer testis antigen, cancer vaccine, DNA methylation, chromatin, immunotherapy
Current Pharmaceutical Design
Title: Circumventing Immune Tolerance Through Epigenetic Modification
Volume: 16 Issue: 3
Author(s): Jason A. Dubovsky, Alejandro Villagra, John J. Powers, Hong-Wei Wang, Javier Pinilla-Ibarz and Eduardo M. Sotomayor
Affiliation:
Keywords: Histone deacetylase, tolerance, cancer testis antigen, cancer vaccine, DNA methylation, chromatin, immunotherapy
Abstract: In recent decades our understanding of immune cell activation and homeostasis has significantly expanded. Such progress helped to better define the cellular, molecular, and epigenetic networks involved in the immune response in the tumor microenvironment and renewed the enthusiasm towards the potential power of cancer immunotherapy. However, successful translation of novel mechanistic discoveries into effective immunotherapy was hindered by a number of obstacles, among them the ability of tumors to tolerize host lymphocytes rendering them functionally incompetent and the tumors ability to evade antigen-specific immune recognition through a variety of genetic, epigenetic, and stromal factors. These immunosuppressive strategies have, thus far, blunted our efforts to effectively unleash anti-cancer immunity. Fortunately, the wealth of new information regarding the interactions between tumors and the immune system and the regulation of certain highly antigenic tumor proteins has led to novel approaches with the potential to render cancer cells helpless towards immune attack. Here we summarize recent findings on cancer-induced T-lymphocyte tolerance and discuss a novel “vaccinate-induce” strategy conceived to counteract these effects at an epigenetic level.
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Cite this article as:
Dubovsky A. Jason, Villagra Alejandro, Powers J. John, Wang Hong-Wei, Pinilla-Ibarz Javier and Sotomayor M. Eduardo, Circumventing Immune Tolerance Through Epigenetic Modification, Current Pharmaceutical Design 2010; 16 (3) . https://dx.doi.org/10.2174/138161210790170120
DOI https://dx.doi.org/10.2174/138161210790170120 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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