Abstract
Immunotherapy has rapidly become one of the most promising therapeutic approaches for cancer patients. While significantly improving patients’ survival, immunotherapy presents a unique toxicity profile. However, a large proportion of patients do not achieve optimal and durable responses, due in part to the lack of specific molecular markers that can comprehensively guide patient and therapeutic selection. Precision medicine, involving therapeutic decisions fine-tuned to the genetic makeup of an individual’s tumor, has the potential to profoundly improve the outcomes of patients treated with immunotherapy. Yet, understanding the influence of genetic variations on immunotherapy is just one aspect of developing precision medicine strategies. Epigenomics, and the advent of optimized epigenetic drugs, is emerging as a powerful tool to expand the potential of precision medicine in cancer immunotherapy. The human epigenome represents an exceptional roadmap providing a wealth of information about specific interactions between an individual’s genetic variations and environmental influences. This chapter is focused on the utility in precision medicine of epigenetic variations in the immune-response and immune-escape, and on potential applications for epigenetic therapies.
Abbreviations
- 5caC:
-
5-carboxylcytosine
- 5fC:
-
5-formylcytosine
- 5hmC:
-
5-hydroxymethylcytosine
- 5mC:
-
5-methylcytosine
- APC:
-
Antigen-presenting cell
- BRD:
-
Bromodomain
- caQTLs:
-
Chromatin accessibility quantitative traits loci
- CGI:
-
CpG island
- cHL:
-
Classical Hodgkin lymphoma
- CIMP:
-
CGI methylator phenotype
- CTA:
-
Cancer testis antigen
- ctDNA:
-
Cell-free circulating tumor DNA
- CTL:
-
Cytotoxic T cells
- CTLA-4:
-
Cytotoxic T lymphocyte-associated protein 4
- DAMP:
-
Damage-associated molecular pattern
- DC:
-
Dendritic cell
- DNMT:
-
DNA methyltransferase
- DNMTi:
-
DNMT inhibitor
- ENCODE:
-
Encyclopedia of DNA Elements
- eQTLs:
-
Expression Quantitative Traits Loci
- EZH2:
-
Enhancer of Zeste Homolog 2
- GWAS:
-
Genome-wide association studies
- HAT:
-
Histone acetyltransferase
- HDAC:
-
Histone deacetylases
- HDACi:
-
HDAC inhibitor
- hmQTLs:
-
Histone modification quantitative traits loci
- HNSCC:
-
Head and neck squamous cell carcinoma
- ICD:
-
Immunogenic cell death
- INF:
-
Interferon
- MBD:
-
Methyl-CpG-binding domain
- MDSC:
-
Myeloid-derived suppressor cells
- meQTLs:
-
Methylation quantitative traits loci
- MHC:
-
Major histocompatibility complex
- MSI:
-
Microsatellite instability
- NK:
-
Natural killer
- NSCLC:
-
Non-small-cell lung cancer
- PD-1:
-
Programmed cell death-1
- PD-L1:
-
Programmed cell Death-Ligand 1
- PTM:
-
Posttranslational modification
- QTL:
-
Quantitative traits loci
- SNP:
-
Single-nucleotide polymorphism
- TAA:
-
Tumor-associated antigens
- TCR:
-
T cell receptor
- TDG:
-
Thymine-DNA glycosylase
- TET:
-
Ten-eleven translocation methylcytosine dioxygenases
- TF:
-
Transcription factor
- tfQTLs:
-
Transcription factor quantitative traits loci
- TME:
-
Tumor microenvironment
- Treg:
-
T regulatory cell
- TSG:
-
Tumor suppressor genes
- TSS:
-
Transcription start site
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Acknowledgments
We are grateful to Dr. Ian Hutchinson for his critical revision of the manuscript and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation for their financial support.
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Orozco, J.I.J., Marzese, D.M., Hoon, D.S.B. (2017). Cancer Epigenomics on Precision Medicine and Immunotherapy. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-31143-2_68-1
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DOI: https://doi.org/10.1007/978-3-319-31143-2_68-1
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