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Cancer Epigenomics on Precision Medicine and Immunotherapy

  • Javier I. J. OrozcoEmail author
  • Diego M. Marzese
  • Dave S. B. Hoon
Reference work entry

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.

Keywords

Neoplasms Epigenomics Immunotherapy Precision Medicine Biomarkers Immunomodulation Histone Deacetylase Inhibitors DNA Methyltransferase Inhibitors 

List of 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

Notes

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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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Javier I. J. Orozco
    • 1
    Email author
  • Diego M. Marzese
    • 1
  • Dave S. B. Hoon
    • 1
  1. 1.Department of Translational Molecular MedicineJohn Wayne Cancer Institute at Providence Saint John’s Health CenterSanta MonicaUSA

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