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Genetic and Epigenetic Biomarkers of Immune Checkpoint Blockade Response

1
Group of Pharmacoepigenetics, Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden
2
Section of Immuno-Oncology, Medical Oncology Service, University Hospitals Regional and Virgen de la Victoria, Biomedical Research Institute of Malaga (IBIMA), 29010 Málaga, Spain
3
Group of Personalized Medicine and Drug Development, Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(1), 286; https://doi.org/10.3390/jcm9010286
Received: 22 November 2019 / Revised: 9 January 2020 / Accepted: 12 January 2020 / Published: 20 January 2020
(This article belongs to the Special Issue Advances and Challenges in Pharmacogenomics)
Checkpoint inhibitor therapy constitutes a promising cancer treatment strategy that targets the immune checkpoints to re-activate silenced T cell cytotoxicity. In recent pivotal trials, immune checkpoint blockade (ICB) demonstrated durable responses and acceptable toxicity, resulting in the regulatory approval of 8 checkpoint inhibitors to date for 15 cancer indications. However, up to ~85% of patients present with innate or acquired resistance to ICB, limiting its clinical utility. Current response biomarker candidates, including DNA mutation and neoantigen load, immune profiles, as well as programmed death-ligand 1 (PD-L1) expression, are only weak predictors of ICB response. Thus, identification of novel, more predictive biomarkers that could identify patients who would benefit from ICB constitutes one of the most important areas of immunotherapy research. Aberrant DNA methylation (5mC) and hydroxymethylation (5hmC) were discovered in multiple cancers, and dynamic changes of the epigenomic landscape have been identified during T cell differentiation and activation. While their role in cancer immunosuppression remains to be elucidated, recent evidence suggests that 5mC and 5hmC may serve as prognostic and predictive biomarkers of ICB-sensitive cancers. In this review, we describe the role of epigenetic phenomena in tumor immunoediting and other immune evasion related processes, provide a comprehensive update of the current status of ICB-response biomarkers, and highlight promising epigenomic biomarker candidates. View Full-Text
Keywords: immunotherapy; predictor; resistance; epigenetics; stroma; melanoma; non-small-cell lung cancer immunotherapy; predictor; resistance; epigenetics; stroma; melanoma; non-small-cell lung cancer
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MDPI and ACS Style

Xiao, Q.; Nobre, A.; Piñeiro, P.; Berciano-Guerrero, M.-Á.; Alba, E.; Cobo, M.; Lauschke, V.M.; Barragán, I. Genetic and Epigenetic Biomarkers of Immune Checkpoint Blockade Response. J. Clin. Med. 2020, 9, 286. https://doi.org/10.3390/jcm9010286

AMA Style

Xiao Q, Nobre A, Piñeiro P, Berciano-Guerrero M-Á, Alba E, Cobo M, Lauschke VM, Barragán I. Genetic and Epigenetic Biomarkers of Immune Checkpoint Blockade Response. Journal of Clinical Medicine. 2020; 9(1):286. https://doi.org/10.3390/jcm9010286

Chicago/Turabian Style

Xiao, Qingyang, André Nobre, Pilar Piñeiro, Miguel-Ángel Berciano-Guerrero, Emilio Alba, Manuel Cobo, Volker M. Lauschke, and Isabel Barragán. 2020. "Genetic and Epigenetic Biomarkers of Immune Checkpoint Blockade Response" Journal of Clinical Medicine 9, no. 1: 286. https://doi.org/10.3390/jcm9010286

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