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Peixoto et al. Cancer Drug Resist 2018;1:219-29 I http://dx.doi.org/10.20517/cdr.2018.17 Page 227

CONCLUSION
Altogether, these recent data clearly demonstrate that, although immune checkpoints and particularly
PD-L1 are frequently overexpressed in tumors compared to healthy tissues, some factors might still be
able to modulate their expression via the regulation of DNA methylation and histone modifications
of their promoters [Figure 2]. Since immunohistochemistry staining are still difficult to quantify and
standardize, mainly because of different antibody specificities, various fixation times and partially subjective
interpretations between different laboratories, we speculate that quantification of promoter methylation
of immune checkpoint inhibitors could be a robust and reproducible alternative method to quickly select
good responsive patients which could be directed towards anti-PD-L1 therapies and those who could be
good candidates for combined therapy using DNA demethylating agents and immunotherapy protocols.
But, further pre-clinical and clinical studies testing the combination of ICB with epidrugs and additional
regulators of immune checkpoint expression will be necessary to evaluate their efficiency to bypass the
immunotherapy resistance in cancers.

DECLARATIONS
Acknowledgements
Peixoto P, Boyer-Guittaut M and Hervouet E are supported by funding from institutional grants from
INSERM, EFS and Univ. Bourgogne Franche-Comté and by the «Ligue Contre le Cancer» (2017),
«Cancéropôle Grand-Est» (OPE-2017-0052/DOC) and «Région Bourgogne-Franche-Comté» (2018).

Authors’ contributions
Wrote the paper: Peixoto P, Hervouet E
Edited the paper: Renaude E, Boyer-Guittaut M

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by funding from institutional grants from INSERM, EFS, and University of
Bourgogne Franche-Comté and by the “Ligue Contre le Cancer” (2017) and the “Région Bourgogne Franche-
Comté” (2014C-15449).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2018.

REFERENCES
1. Peng D, Kryczek I, Nagarsheth N, Zhao L, Wei S, et al. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and
immunotherapy. Nature 2015;527:249-53.
2. Berghuis D, Santos SJ, Baelde HJ, Taminiau AH, Egeler RM, et al. Pro-inflammatory chemokine-chemokine receptor interactions