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oai:repisalud.isciii.es:20.500.12105/179902024-11-28T15:37:50Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Xiao, Qingyang author Nobre, André author Piñeiro, Pilar author Berciano-Guerrero, Miguel-Ángel author Alba, Emilio author Cobo, Manuel author Lauschke, Volker M. author Barragán, Isabel authoraffiliation [Xiao,Q; Nobre,A; Berciano-Guerrero,MA; Barragán,I] Group of Pharmacoepigenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. [Xiao,Q; Piñeiro,P; Berciano-Guerrero,MA; Alba,E; Cobo,M; Barragán,I] Section of Immuno-Oncology, Medical Oncology Service, University Hospitals Regional and Virgen de la Victoria, Biomedical Research Institute of Malaga (IBIMA), Málaga, Spain. [Lauschke,VM] Group of Personalized Medicine and Drug Development, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. 2024-02-12T19:45:10Z 2024-02-12T19:45:10Z 2020-01-20 10.3390/jcm9010286 2077-0383 Journal of Clinical Medicine http://hdl.handle.net/10668/3626 31968651 http://hdl.handle.net/20.500.12105/17990 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. eng Immunotherapy Predictor Resistance Epigenetics Stroma Melanoma Non-small-cell lung cancer Inmunoterapia Predicción Inhibidores de puntos de control inmunológico Epigenómica Carcinoma, non-small-cell lung Genetic and Epigenetic Biomarkers of Immune Checkpoint Blockade Response review article