title: Molecular Pathways: At the Crossroads of Cancer Epigenetics and Immunotherapy.
abstract: Epigenetic regulation allows heritably modulating gene expression profiles without modifying the primary sequence of gDNA. Under physiologic conditions, epigenetic patterns determine tissue-specific gene expression landscapes, gene imprinting, inactivation of chromosome X, and preservation of genomic stability. The most characterized mediators of epigenetic inheritance are gDNA methylation and histone posttranslational modifications that cooperate to alter chromatin state and genome transcription. According to these notions, it is not surprising that cancer cells invariantly deploy epigenetic alterations to achieve gene expression patterns required for neoplastic transformation and tumor progression. In this context, the recently uncovered use of epigenetic alterations by cancer cells to become stealth from the host's immune recognition has significant immunobiologic relevance in tumor progression, and it appears to have potential clinical usefulness. Indeed, immune evasion is among the major obstacles to further improve the efficacy of cancer immunotherapies and to increase long-lasting disease control. Luckily, different "epigenetic drugs" able to revert these "epimutations" are available, some of which have already been approved for clinical use. Here, we summarize the immunomodulatory activities of epigenetic drugs that lead to improved immune recognition of cancer cells and focus on the potential of this class of agents in improving the anticancer activity of novel immunotherapies through combinatorial epigenetic immunotherapy approaches.
authors.affiliation: Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy. mmaiocro@gmail.com.
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.affiliation: Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Covre
authors.affiliation: Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Fratta
authors.affiliation: Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giacomo
authors.affiliation: ASTEX Pharmaceuticals Inc., Pleasanton, California.
authors.forename: Pietro
authors.initials: P
authors.lastname: Taverna
authors.affiliation: Regina Elena National Cancer Institute, Roma, Italy.
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Natali
authors.affiliation: Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Coral
authors.affiliation: Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Sigalotti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D002843:Chromatin / Q000378:metabolism; D002986:Clinical Trials as Topic; D019175:DNA Methylation; D018450:Disease Progression; D044127:Epigenesis, Genetic; D057890:Epigenomics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin