Cited by 102Cancer Immunotherapy and BiomarkersEpigenetics and DNA MethylationImmunotherapy and Immune Responses

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Epigenetic drugs as immunomodulators for combination therapies in solid tumors

Sigalotti, Luca, Fratta, Elisabetta, Coral, Sandra, Maio, Michele·2014·Pharmacology & Therapeutics

DOI 10.1016/j.pharmthera.2013.12.015

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Abstract

Continuously improving knowledge of the fine mechanisms regulating cross-talk between immune cells, and of their multi-faceted interactions with cancer cells, has prompted the development of several novel immunotherapeutic strategies for cancer treatment. Among these, modulation of the host's immune system by targeting immunological synapses has shown notable clinical efficacy in different tumor types. Despite this, objective clinical responses and, more importantly, long-term survival are achieved only by a fraction of patients; therefore, identification of the mechanism(s) responsible for the differential effectiveness of immune checkpoint blockade in specific patient populations is an area of intense investigation. Neoplastic cells can activate multiple mechanisms to escape from immune control; among these, epigenetic reprogramming is emerging as a key player. Selected tumor-associated antigens, Human Leukocyte Antigens, and accessory/co-stimulatory molecules required for efficient recognition of neoplastic cells by the immune system have been shown to be epigenetically silenced or down-regulated in cancer. Consistent with the inherent reversibility of epigenetic silencing, "epigenetic" drugs, such as inhibitors of DNA methyltransferases and of histone deacetylases, can restore the functional expression of these down-regulated molecules, thus improving the recognition of cancer cells by both the innate and adaptive immune responses. This review focuses on the immunomodulatory activity of epigenetic drugs and on their proposed clinical use in novel combined chemo-immunotherapeutic regimens for the treatment of solid tumors.

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Authors: Sigalotti, L., Fratta, E., Coral, S., & Maio, M.
Affiliations: Centro di Riferimento Oncologico (IT)
University of Siena (IT)
Corresponding author: Maio, Michele
ORCID: Sigalotti, Luca
Fratta, Elisabetta
Coral, Sandra
Maio, Michele
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 2014-06
Volume: 142
Issue: 3
Pages: 339-350
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/j.pharmthera.2013.12.015
OpenAlex: W2019173523
Cited by: 102
References: 152
Citations by year: 2026: 1 · 2025: 3 · 2024: 4 · 2023: 11 · 2022: 5 · 2021: 14 · 2020: 6 · 2019: 12 · 2018: 13 · 2017: 7 · 2016: 13 · 2015: 7 · 2014: 6
FWCI: 1.25
Type: journal article
Language: en
Open access: closed
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Use Siena air (University of Siena) (submittedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: epigenetic drugs, immunomodulation, solid tumors, hypomethylating agents, histone deacetylase inhibitors, epigenetic silencing, immune checkpoint blockade, tumor immune evasion, tumor-associated antigens, costimulatory molecules, immunological synapse, cancer immunotherapy
MeSH terms: Animals, Humans, Immunologic Factors, Immunotherapy, Neoplasms, RNA Editing, Antigen Presentation, Epigenesis, Genetic

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Epigenetic drugs as immunomodulators for combination therapies in solid tumors

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