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Cancer Epigenomics on Precision Medicine and Immunotherapy

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Handbook of Nutrition, Diet, and Epigenetics

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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.

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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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Authors and Affiliations

  1. Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John’s Health Center, Santa Monica, CA, USA

    Javier I. J. Orozco, Diego M. Marzese & Dave S. B. Hoon

Authors
  1. Javier I. J. Orozco
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  2. Diego M. Marzese
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  3. Dave S. B. Hoon
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Corresponding author

Correspondence to Javier I. J. Orozco .

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Editors and Affiliations

  1. School of Life Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. Diabetes and Nutritional Sciences Research Division, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Victor R. Preedy

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Orozco, J.I.J., Marzese, D.M., Hoon, D.S.B. (2019). Cancer Epigenomics on Precision Medicine and Immunotherapy. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-55530-0_68

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  • DOI: https://doi.org/10.1007/978-3-319-55530-0_68

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