Xiao, QingyangNobre, AndréPiñeiro, PilarBerciano-Guerrero, Miguel-ÁngelAlba, EmilioCobo, ManuelLauschke, Volker M.Barragán, Isabel2022-05-112022-05-112020-01-20Xiao Q, Nobre A, Piñeiro P, Berciano-Guerrero MÁ, Alba E, Cobo M, et al. Genetic and Epigenetic Biomarkers of Immune Checkpoint Blockade Response. J Clin Med. 2020 Jan 20;9(1):286http://hdl.handle.net/10668/3626Checkpoint 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/ImmunotherapyPredictorResistanceEpigeneticsStromaMelanomaNon-small-cell lung cancerCarcinoma, non-small-cell lungMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::EpigenomicsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::PrognosisMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA MethylationMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Immune EvasionMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::ImmunotherapyMedical Subject Headings::Diseases::NeoplasmsMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological MarkersMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::MutationMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, GeneticMedical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-LymphocytesMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNAreview article31968651open accessInmunoterapiaPredicciónInhibidores de puntos de control inmunológicoEpigenómica10.3390/jcm90102862077-0383PMC7019273