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Epigenomes
Special Issues
Epigenetics and Immune Checkpoints
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Epigenetics and Immune Checkpoints

A special issue of Epigenomes (ISSN 2075-4655).

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 11152

Special Issue Editors

Dr. Alessia Covre

E-Mail Website
Guest Editor
Center for Immuno-Oncology, Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena and University of Siena, Siena, Italy.
Interests: cancer epigenetics; immunotherapy
Dr. Elisabetta Fratta

E-Mail
Guest Editor
Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico, Aviano, Italy
Interests: cancer epigenetics; ncRNAs; immunotherapy; targeted therapy

Special Issue Information

Dear Colleagues,

The epigenetic immune modeling of cancer cells represents a key hallmark of cancer, as it impairs the host’s functional immune recognition of malignant cells. The pharmacologic targeting of epigenetic alteration with epigenetic drugs has been demonstrated to possess significant immunomodulatory properties, sensitizing tumor cells to emerging immunotherapies.

Targeting immune checkpoint(s) with immunomodulatory monoclonal antibodies (mAbs) is a novel and rapidly evolving strategy to treat cancer, and is rapidly spreading to different tumor histologies.

Despite this unprecedented efficacy, a significant proportion of cancer patients do not achieve tumor regression due to primary resistance, or develop secondary resistance to anti-immune-checkpoint treatment over time.

Therefore, it is essential to identify new mechanism(s) underlying treatment failure(s) and design novel epigenetic-based combination therapeutic approaches to overcome primary/secondary resistance, in order to improve the overall efficacy of immune-checkpoint-blocking mAb therapy. In addition, novel biomarkers for the prediction of the response to immune-checkpoint inhibitors are urgently needed to stratify cancer patients who would benefit most from this treatment. In this context, epigenetic biomarkers would represent a valuable tool to predict response to immunotherapy, thus offering more personalized therapeutic regimens. Therefore, the aim of this Special Issue is to present a collection of the latest research regarding the role that epigenetics plays in improving cancer immunotherapy, and the utility that it offers in defining new potential therapeutic targets and cancer biomarkers.

Dr. Alessia Covre
Dr. Elisabetta Fratta
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Epigenomes is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • epigenetics
  • immune-checkpoint inhibitors
  • epigenetic therapies
  • biomarkers

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Published Papers (2 papers)

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Research

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15 pages, 2657 KiB  
Article
Epigenetic Immune Remodeling of Mesothelioma Cells: A New Strategy to Improve the Efficacy of Immunotherapy
by Maria Fortunata Lofiego, Sara Cannito, Carolina Fazio, Francesca Piazzini, Ornella Cutaia, Laura Solmonese, Francesco Marzani, Carla Chiarucci, Anna Maria Di Giacomo, Luana Calabrò, Sandra Coral, Michele Maio, Alessia Covre and on behalf of the EPigenetic Immune-Oncology Consortium Airc (EPICA) Investigators
Epigenomes 2021, 5(4), 27; https://doi.org/10.3390/epigenomes5040027 - 14 Dec 2021
Cited by 4 | Viewed by 4390
Abstract
Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a severe prognosis, and with a long-standing need for more effective therapeutic approaches. However, treatment with immune checkpoint inhibitors is becoming an increasingly effective strategy for MPM patients. In this scenario, epigenetic modifications may [...] Read more.
Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a severe prognosis, and with a long-standing need for more effective therapeutic approaches. However, treatment with immune checkpoint inhibitors is becoming an increasingly effective strategy for MPM patients. In this scenario, epigenetic modifications may negatively regulate the interplay between immune and malignant cells within the tumor microenvironment, thus contributing to the highly immunosuppressive contexture of MPM that may limit the efficacy of immunotherapy. Aiming to further improve prospectively the clinical efficacy of immunotherapeutic approaches in MPM, we investigated the immunomodulatory potential of different classes of epigenetic drugs (i.e., DNA hypomethylating agent (DHA) guadecitabine, histone deacetylase inhibitors VPA and SAHA, or EZH2 inhibitors EPZ-6438) in epithelioid, biphasic, and sarcomatoid MPM cell lines, by cytofluorimetric and real-time PCR analyses. We also characterized the effects of the DHA, guadecitabine, on the gene expression profiles (GEP) of the investigated MPM cell lines by the nCounter platform. Among investigated drugs, exposure of MPM cells to guadecitabine, either alone or in combination with VPA, SAHA and EPZ-6438 demonstrated to be the main driver of the induction/upregulation of immune molecules functionally crucial in host-tumor interaction (i.e., HLA class I, ICAM-1 and cancer testis antigens) in all three MPM subtypes investigated. Additionally, GEP demonstrated that treatment with guadecitabine led to the activation of genes involved in several immune-related functional classes mainly in the sarcomatoid subtype. Furthermore, among investigated MPM subtypes, DHA-induced CDH1 expression that contributes to restoring the epithelial phenotype was highest in sarcomatoid cells. Altogether, our results contribute to providing the rationale to develop new epigenetically-based immunotherapeutic approaches for MPM patients, potentially tailored to the specific histologic subtypes. Full article
(This article belongs to the Special Issue Epigenetics and Immune Checkpoints)
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Review

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25 pages, 2035 KiB  
Review
Can Immune Suppression and Epigenome Regulation in Placenta Offer Novel Insights into Cancer Immune Evasion and Immunotherapy Resistance?
by Sultana Mehbuba Hossain, Chiemi F. Lynch-Sutherland, Aniruddha Chatterjee, Erin C. Macaulay and Michael R. Eccles
Epigenomes 2021, 5(3), 16; https://doi.org/10.3390/epigenomes5030016 - 25 Jul 2021
Cited by 5 | Viewed by 5741
Abstract
Cancer is the second leading cause of mortality and morbidity in the developed world. Cancer progression involves genetic and epigenetic alterations, accompanied by aggressive changes, such as increased immune evasion, onset of metastasis, and drug resistance. Similar to cancer, DNA hypomethylation, immune suppression, [...] Read more.
Cancer is the second leading cause of mortality and morbidity in the developed world. Cancer progression involves genetic and epigenetic alterations, accompanied by aggressive changes, such as increased immune evasion, onset of metastasis, and drug resistance. Similar to cancer, DNA hypomethylation, immune suppression, and invasive cell behaviours are also observed in the human placenta. Mechanisms that lead to the acquisition of invasive behaviour, immune evasion, and drug and immunotherapy resistance are presently under intense investigations to improve patient outcomes. Here, we review current knowledge regarding the similarities between immune suppression and epigenome regulation, including the expression of repetitive elements (REs), endogenous retroviruses (ERVs) and transposable elements (TEs) in cells of the placenta and in cancer, which are associated with changes in immune regulation and invasiveness. We explore whether immune suppression and epigenome regulation in placenta offers novel insights into immunotherapy resistance in cancer, and we also discuss the implications and the knowledge gaps relevant to these findings, which are rapidly being accrued in these quite disparate research fields. Finally, we discuss potential linkages between TE, ERV and RE activation and expression, regarding mechanisms of immune regulation in placenta and cancer. A greater understanding of the role of immune suppression and associated epigenome regulation in placenta could help to elucidate some comparable mechanisms operating in cancer, and identify potential new therapeutic targets for treating cancer. Full article
(This article belongs to the Special Issue Epigenetics and Immune Checkpoints)
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