RT Journal Article
T1 Genetic and Epigenetic Biomarkers of Immune Checkpoint Blockade Response
A1 Xiao, Qingyang
A1 Nobre, André
A1 Piñeiro, Pilar
A1 Berciano-Guerrero, Miguel-Ángel
A1 Alba, Emilio
A1 Cobo, Manuel
A1 Lauschke, Volker M.
A1 Barragán, Isabel
K1 Immunotherapy
K1 Predictor
K1 Resistance
K1 Epigenetics
K1 Stroma
K1 Melanoma
K1 Non-small-cell lung cancer
K1 Carcinoma, non-small-cell lung
AB 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.
PB MDPI
YR 2020
FD 2020-01-20
LK http://hdl.handle.net/10668/3626
UL http://hdl.handle.net/10668/3626
LA en
NO Xiao 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):286
DS RISalud
RD Apr 18, 2025