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Epigenetic regulation of immune escape genes in cancer
Thomas B Tomasi1, William J Magner, A Nazmul H Khan
1Department of Immunology, Laboratory of Molecular Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. thomas.tomasi@roswellpark.org
Abstract:
According to the concept of immune surveillance, the appearance of a tumor indicates that it has earlier evaded host defenses and subsequently must have escaped immunity to evolve into a full-blown cancer. Tumor escape mechanisms have focused mainly on mutations of immune and apoptotic pathway genes. However, data obtained over the past few years suggest that epigenetic silencing in cancer may be as frequent a cause of gene inactivation as are mutations. Here, we discuss the evidence that tumor immune evasion is mediated by non-mutational epigenetic events involving chromatin and that epigenetics collaborates with mutations in determining tumor progression. Since epigenetic changes are potentially reversible, the relative contribution of mutations and epigenetics, to the gene defects in any given tumor, may be a factor in determining the efficacy of treatments. We review new developments in basic chromatin mechanisms and in this context describe the rationale for the current use of epigenetic agents in cancer therapy and for a novel epigenetically generated tumor vaccine model. We emphasize that epigenetic cancer treatments are currently a 'blunt-sword' and suggest future directions for designing chromatin-based programs of potential value in the diagnosis and treatment of cancer.
Insights
Cancer cells evade immune surveillance through epigenetic silencing, not just mutations. Understanding this epigenetic role is key for developing effective, potentially reversible cancer therapies and vaccines.
Area of Science:
- Oncology
- Epigenetics
- Immunology
Background:
- Tumorigenesis involves immune evasion, traditionally attributed to gene mutations.
- Epigenetic silencing is emerging as a significant mechanism for gene inactivation in cancer, comparable to mutations.
Purpose of the Study:
- To review evidence linking non-mutational epigenetic events involving chromatin to tumor immune evasion.
- To explore the collaborative role of epigenetics and mutations in cancer progression.
- To discuss the implications of epigenetic reversibility for cancer treatment efficacy.
Main Methods:
- Review of current scientific literature on chromatin mechanisms and epigenetic silencing in cancer.
- Analysis of data supporting epigenetic mediation of tumor immune evasion.
- Examination of the rationale for current epigenetic cancer therapies and novel vaccine models.
Main Results:
- Epigenetic modifications, particularly chromatin alterations, play a crucial role in tumor immune evasion.
- Epigenetics and mutations cooperate in driving tumor progression.
- The reversible nature of epigenetic changes offers potential therapeutic advantages.
Conclusions:
- Epigenetic mechanisms are critical drivers of cancer immune evasion and progression.
- Epigenetic therapies hold promise but require refinement for greater precision.
- Future research should focus on developing sophisticated chromatin-based strategies for cancer diagnosis and treatment.
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