Epigenetics, a key player of immunotherapy resistance

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

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