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Epigenetic Genes, Biomarkers and Immunotherapy in Cancers
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Epigenetic Genes, Biomarkers and Immunotherapy in Cancers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 7109

Special Issue Editors

Dr. Urszula Oleksiewicz

E-Mail Website
Guest Editor
Department of Cancer Immunology, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Poznan, Poland
Interests: iPS; stem cells; stemness; pluripotency; self-renewal; epigenetics; differentiation; KRAB-ZFPs; cancer; epigenetic repressor; ZNF471; ZBRK1; ZKSCAN3; ZNF300; ZFP57; ZNF224; TRIM28; KAP1
Prof. Dr. Andrzej Mackiewicz

E-Mail Website
Co-Guest Editor
1. Department of Medical Biotechnology, Poznan University of Medical Sciences, 61-866 Poznan, Poland
2. Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Center, 61-866 Poznan, Poland
Interests: melanoma; melanoma vaccines; cancer stem cells; melanoma stem cells; cancer immunotherapy; cancer immunology; acute-phase response; IL-6; soluble IL-6 receptor; immunotherapy clinical trials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immunotherapies that boost the immune system response against cancer cells show promising effects in experimental and clinical setups. A wide-ranging portfolio of immunotherapy options that are available or under development include immune checkpoint blocking antibodies, chimeric antigen vector (CAR) T cells, vaccines based on dendritic cells or engineered cancer cells, etc. Nevertheless, in certain cases, the efficacy of such a treatment may be compromised due to the limited response within tumors with immunosuppressive features or toxic auto-immune responses.

Epigenetic modifications (i.e., DNA methylation, histone modifications, and ncRNAs) shape the transcriptional profile of tumor and immune cells, thus affecting tumor–immune system interactions. Certain immune signaling molecules were shown to be epigenetically regulated, e.g., via aberrant promoter hypermethylation or EZH2-mediated H3K37me3 deposition. Reversing their epigenetic status with epigenetic drugs, such as DNA or histone methyltransferase inhibitors, restores their expression, thus resulting in increased tumor immunogenicity. As such, epigenetic modifications within specific immune-related loci may act as biomarkers of the immunotherapy response but may also serve as targets supporting immunotherapy. Moreover, epigenetic modifications may be involved in the transcriptional activation of endogenous retroviruses, which evoke a dsRNA-mediated IFN response engaged in anti-cancer immunity.

For this Special Issue, we invite the original papers, reviews, comments, and other article types that focus on epigenetic genes and modifications that may modulate the response to tumor immunotherapy. We welcome the papers focused on the epigenetic genes or machineries that may affect tumor–immune interactions, epigenetic biomarkers that may guide immunotherapy management, and epigenetic targets and drugs that may reinforce immunotherapies. We also welcome articles on epigenetic biomarkers and genes with a role in cancer, as well as the articles on current findings associated with cancer immunotherapy.

Dr. Urszula Oleksiewicz
Prof. Dr. Andrzej Mackiewicz
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • epigenetics
  • epigenetic modifications
  • immunotherapies
  • immune checkpoint
  • DNA methylation
  • histone modifications
  • epigenetic biomarkers
  • epidrugs
  • endogenous retroviruses

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Published Papers (5 papers)

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Research

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26 pages, 9314 KiB  
Article
The Epigenetic Modifiers HDAC2 and HDAC7 Inversely Associate with Cancer Stemness and Immunity in Solid Tumors
by Kacper Maciejewski, Marek Giers, Urszula Oleksiewicz and Patrycja Czerwinska
Int. J. Mol. Sci. 2024, 25(14), 7841; https://doi.org/10.3390/ijms25147841 - 17 Jul 2024
Viewed by 1275
Abstract
Dysregulation of histone deacetylases (HDACs) is closely associated with cancer development and progression. Here, we comprehensively analyzed the association between all HDAC family members and several clinicopathological and molecular traits of solid tumors across 22 distinct tumor types, focusing primarily on cancer stemness [...] Read more.
Dysregulation of histone deacetylases (HDACs) is closely associated with cancer development and progression. Here, we comprehensively analyzed the association between all HDAC family members and several clinicopathological and molecular traits of solid tumors across 22 distinct tumor types, focusing primarily on cancer stemness and immunity. To this end, we used publicly available TCGA data and several bioinformatic tools (i.e., GEPIA2, TISIDB, GSCA, Enrichr, GSEA). Our analyses revealed that class I and class II HDAC proteins are associated with distinct cancer phenotypes. The transcriptomic profiling indicated that class I HDAC members, including HDAC2, are positively associated with cancer stemness, while class IIA HDAC proteins, represented by HDAC7, show a negative correlation to cancer stem cell-like phenotypes in solid tumors. In contrast to tumors with high amounts of HDAC7 proteins, the transcriptome signatures of HDAC2-overexpressing cancers are significantly enriched with biological terms previously determined as stemness-associated genes. Moreover, high HDAC2-expressing tumors are depleted with immune-related processes, and HDAC2 expression correlates with tumor immunosuppressive microenvironments. On the contrary, HDAC7 upregulation is significantly associated with enhanced immune responses, followed by enriched infiltration of CD4+ and CD8+ T cells. This is the first comprehensive report demonstrating robust and versatile associations between specific HDAC family members, cancer dedifferentiation, and anti-tumor immune statuses in solid tumors. Full article
(This article belongs to the Special Issue Epigenetic Genes, Biomarkers and Immunotherapy in Cancers)
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Review

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18 pages, 545 KiB  
Review
Programmed Cell Death Ligand 1 (PD-L1) Immunohistochemical Expression in Advanced Urothelial Bladder Carcinoma: An Updated Review with Clinical and Pathological Implications
by Emanuela Germanà, Ludovica Pepe, Cristina Pizzimenti, Mariagiovanna Ballato, Francesco Pierconti, Giovanni Tuccari, Antonio Ieni, Giuseppe Giuffrè, Guido Fadda, Vincenzo Fiorentino and Maurizio Martini
Int. J. Mol. Sci. 2024, 25(12), 6750; https://doi.org/10.3390/ijms25126750 - 19 Jun 2024
Cited by 1 | Viewed by 1166
Abstract
The management of advanced bladder carcinoma involves a multidisciplinary approach, but the prognosis remains poor for many patients. The immune system plays a crucial role in this disease, influencing both tumor development and response to treatment, and exploiting the immune system against the [...] Read more.
The management of advanced bladder carcinoma involves a multidisciplinary approach, but the prognosis remains poor for many patients. The immune system plays a crucial role in this disease, influencing both tumor development and response to treatment, and exploiting the immune system against the tumor can be a valuable strategy to destroy neoplastic cells. This is the biological principle underlying Bacillus Calmette–Guérin (BCG) use and, more recently, immune checkpoint inhibitors (ICIs), like PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) inhibitors. In fact, one of the best studied immune checkpoints is represented by the PD-1/PD-L1 axis, which is a well-known immune escape system adopted by neoplastic bladder cells. PD-L1 expression has been associated with a higher pathologic stage and has shown prognostic value in bladder carcinoma. Interestingly, high-grade bladder cancers tend to express higher levels of PD-1 and PD-L1, suggesting a potential role of such an axis in mediating disease progression. Immunotherapy with PD-1 and PD-L1 inhibitors has therefore emerged as a valuable treatment option and has shown efficacy in advanced bladder cancer patients, with high PD-L1 expression levels associated with better treatment responses. Our review aims to provide a comprehensive overview of the role of PD-L1 in advanced bladder cancer, focusing on its implications for treatment decisions and the prediction of treatment response. Overall, our work aims to contribute to the understanding of PD-L1 as a predictive biomarker and highlight its role in shaping therapeutic approaches for advanced bladder cancer. Full article
(This article belongs to the Special Issue Epigenetic Genes, Biomarkers and Immunotherapy in Cancers)
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14 pages, 1366 KiB  
Review
Immunotherapy Based on Immune Checkpoint Molecules and Immune Checkpoint Inhibitors in Gastric Cancer–Narrative Review
by Agata Poniewierska-Baran, Karolina Sobolak, Paulina Niedźwiedzka-Rystwej, Paulina Plewa and Andrzej Pawlik
Int. J. Mol. Sci. 2024, 25(12), 6471; https://doi.org/10.3390/ijms25126471 - 12 Jun 2024
Cited by 3 | Viewed by 1426
Abstract
Due to its rapid progression to advanced stages and highly metastatic properties, gastric cancer (GC) is one of the most aggressive malignancies and the fourth leading cause of cancer-related deaths worldwide. The metastatic process includes local invasion, metastasis initiation, migration with colonisation at [...] Read more.
Due to its rapid progression to advanced stages and highly metastatic properties, gastric cancer (GC) is one of the most aggressive malignancies and the fourth leading cause of cancer-related deaths worldwide. The metastatic process includes local invasion, metastasis initiation, migration with colonisation at distant sites, and evasion of the immune response. Tumour growth involves the activation of inhibitory signals associated with the immune response, also known as immune checkpoints, including PD-1/PD-L1 (programmed death 1/programmed death ligand 1), CTLA-4 (cytotoxic T cell antigen 4), TIGIT (T cell immunoreceptor with Ig and ITIM domains), and others. Immune checkpoint molecules (ICPMs) are proteins that modulate the innate and adaptive immune responses. While their expression is prominent on immune cells, mainly antigen-presenting cells (APC) and other types of cells, they are also expressed on tumour cells. The engagement of the receptor by the ligand is crucial for inhibiting or stimulating the immune cell, which is an extremely important aspect of cancer immunotherapy. This narrative review explores immunotherapy, focusing on ICPMs and immune checkpoint inhibitors in GC. We also summarise the current clinical trials that are evaluating ICPMs as a target for GC treatment. Full article
(This article belongs to the Special Issue Epigenetic Genes, Biomarkers and Immunotherapy in Cancers)
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20 pages, 692 KiB  
Review
circRNAs in Endometrial Cancer—A Promising Biomarker: State of the Art
by Karolina Włodarczyk, Weronika Kuryło, Anna Pawłowska-Łachut, Wiktoria Skiba, Dorota Suszczyk, Paulina Pieniądz, Małgorzata Majewska, Ewa Boniewska-Bernacka and Iwona Wertel
Int. J. Mol. Sci. 2024, 25(12), 6387; https://doi.org/10.3390/ijms25126387 - 9 Jun 2024
Cited by 1 | Viewed by 1413
Abstract
Endometrial cancer (EC) is one of the most common malignant tumors among women in the 21st century, whose mortality rate is increasing every year. Currently, the diagnosis of EC is possible only after a biopsy. However, it is necessary to find a new [...] Read more.
Endometrial cancer (EC) is one of the most common malignant tumors among women in the 21st century, whose mortality rate is increasing every year. Currently, the diagnosis of EC is possible only after a biopsy. However, it is necessary to find a new biomarker that will help in both the diagnosis and treatment of EC in a non-invasive way. Circular RNAs (circRNAs) are small, covalently closed spherical and stable long non-coding RNAs (lncRNAs) molecules, which are abundant in both body fluids and human tissues and are expressed in various ways. Considering the new molecular classification of EC, many studies have appeared, describing new insights into the functions and mechanisms of circRNAs in EC. In this review article, we focused on the problem of EC and the molecular aspects of its division, as well as the biogenesis, functions, and diagnostic and clinical significance of circRNAs in EC. Full article
(This article belongs to the Special Issue Epigenetic Genes, Biomarkers and Immunotherapy in Cancers)
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Other

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11 pages, 3384 KiB  
Perspective
hTERT Epigenetics Provides New Perspectives for Diagnosis and Evidence-Based Guidance of Chemotherapy in Cancer
by Simeon Santourlidis, Marcos J. Araúzo-Bravo, Robert T. Brodell, Mohamed Hassan and Marcelo L. Bendhack
Int. J. Mol. Sci. 2024, 25(13), 7331; https://doi.org/10.3390/ijms25137331 - 4 Jul 2024
Viewed by 1158
Abstract
Strong epigenetic pan-cancer biomarkers are required to meet several current, urgent clinical needs and to further improve the present chemotherapeutic standard. We have concentrated on the investigation of epigenetic alteration of the hTERT gene, which is frequently epigenetically dysregulated in a number of [...] Read more.
Strong epigenetic pan-cancer biomarkers are required to meet several current, urgent clinical needs and to further improve the present chemotherapeutic standard. We have concentrated on the investigation of epigenetic alteration of the hTERT gene, which is frequently epigenetically dysregulated in a number of cancers in specific developmental stages. Distinct DNA methylation profiles were identified in our data on early urothelial cancer. An efficient EpihTERT assay could be developed utilizing suitable combinations with sequence-dependent thermodynamic parameters to distinguish between differentially methylated states. We infer from this data set, the epigenetic context, and the related literature that a CpG-rich, 2800 bp region, a prominent CpG island, surrounding the transcription start of the hTERT gene is the crucial epigenetic zone for the development of a potent biomarker. In order to accurately describe this region, we have named it “Acheron” (Ἀχέρων). In Greek mythology, this is the river of woe and misery and the path to the underworld. Exploitation of the DNA methylation profiles focused on this region, e.g., idiolocal normalized Methylation Specific PCR (IDLN-MSP), opens up a wide range of new possibilities for diagnosis, determination of prognosis, follow-up, and detection of residual disease. It may also have broad implications for the choice of chemotherapy. Full article
(This article belongs to the Special Issue Epigenetic Genes, Biomarkers and Immunotherapy in Cancers)
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