Page 31 - Read Online

Peixoto et al. Cancer Drug Resist 2018;1:219-29 Cancer
DOI: 10.20517/cdr.2018.17 Drug Resistance

Review Open Access

Epigenetics, a key player of immunotherapy
resistance

Paul Peixoto , Elodie Renaude , Michaël Boyer-Guittaut , Eric Hervouet 1,2,3
1,2
1
1,3
1 UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, University of Bourgogne Franche-Comté,
INSERM, EFS Bourgogne Franche-Comté, Besançon F-25000, France.
2 EPIGENEXP platform, University of Bourgogne Franche-Comté, Besançon F-25000, France.
3 DImaCell platform, University of Bourgogne Franche-Comté, Besançon F-25000, France.
Correspondence to: Dr. Eric Hervouet, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique,
University of Bourgogne Franche-Comté, INSERM, EFS Bourgogne Franche-Comté, Besançon F-25000, France.
E-mail: eric.hervouet@univ-fcomte.fr

How to cite this article: Peixoto P, Renaude E, Boyer-Guittaut M, Hervouet E. Epigenetics, a key player of immunotherapy
resistance. Cancer Drug Resist 2018;1:219-29. http://dx.doi.org/10.20517/cdr.2018.17

Received: 5 Oct 2018 First Decision: 20 Nov 2018 Revised: 26 Nov 2018 Accepted: 30 Nov 2018 Published: 19 Dec 2018
Science Editors: Godefridus J. Peters, Aamir Ahmad Copy Editor: Cui Yu Production Editor: Huan-Liang Wu

Abstract
In 2018, the Nobel Prize in medicine was awarded to James P. Allison and Tasuku Honjo for their work on the description
of immune checkpoint inhibitors which contributed to the development of new anti-cancer immunotherapies. However,
although these new therapeutic strategies, which are designed to limit immune escape of cancer cells, have been used
or tested successfully in many different cancers, a large proportion of patients have been described to resist and not
respond to these new treatments. The new incoming challenge is now therefore to overcome these resistance and
new recent data presented epigenetic modifications as promising targets to restore anti-tumor immunity. Indeed, both
DNA methylation and post-translational histone modifications have been described to regulate immune checkpoint
inhibitor expression, tumor-associated antigen presentation or cancer cell editing by the immune system and therefore
establishing epigenetic drugs as a potential complement to immunotherapies to improve their efficiency.

Keywords: Epigenetics, DNA methylation, drug resistance, immunotherapy, programed cell death 1, programed cell
death ligand 1, cancer

INTRODUCTION
Antigen presentation by the professional antigen-presenting cells (APCs) are normally recognized by
immune cells via a surface T-cell receptor (TCR), leading to the induction of naive CD8 T-cell clonal
+
expansion and differentiation and finally resulting in the cell death of APCs. Specific tumor-associated
antigens (TAAs) expressed by cancer cells can be identified by the immune system and results in the

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

www.cdrjournal.com