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Epigenetics and Immunotherapy in Cancer
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Epigenetics and Immunotherapy in Cancer

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 January 2025 | Viewed by 8710

Special Issue Editor

Prof. Dr. Luca Sigalotti

E-Mail Website
Guest Editor
IRCCS Centro Di Riferimento Oncologico Aviano, 33081 Aviano, Italy
Interests: cancer epigenetics; cancer genetics; epigenetic therapy; immunotherapy; immunomodulation; sarcoma; melanoma

Special Issue Information

Dear Colleagues,

Cancer is a multifactorial disease, the occurrence of which depends on the the deregulation of key homeostatic systems that control cell behaviour. Among the hallmarks of cancer, most recent research has demonstrated that aberrant epigenetic changes play a fundamental role in providing cancer cells with the means of achieving neoplastic features and expressing aggressive phenotypes. The importance of such phenomena has gained further support from the use of next-generation sequencing technologies to unveil frequent alterations in epigenetic-related genes. Among tumor hallmarks impacted by altered epigenetics, immune recognition of cancer cells has a paramount relevance in view of the key role of the immune system in controlling and eradicating cancer cells. This is also important when considering the game-changing results achieved by immunotherapy, with immune checkpoint inhibitors discovered in several pathologies. In this respect, recent findings have demonstrated that mutations in epigenetic genes profoundly impair immune response and that epigenetic drugs can improve immunogenicity and the immune recognition of cancer cells by acting both on tumor and host side.

Hence, Leading by Prof. Dr. Luca Sigalotti and assisting by our Topical Advisory Panel Member Dr. Walid Shalata (Ben-Gurion University), this Special Issue aims to present the most recent advances in cancer epigenetics, with a special focus on its relation to the regulation of immune-related genes, immunomodulation and immunotherapy.

Prof. Dr. Luca Sigalotti
Guest Editor

Manuscript Submission Information

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Keywords

  • epigenetics
  • DNA methylation
  • non-coding RNA
  • chromatin modification
  • epigenetic drugs
  • immunotherapy
  • tumor immunology
  • innate immune response
  • adaptive immune response
  • immune checkpoints

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Published Papers (4 papers)

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12 pages, 535 KiB  
Article
Circulating miR-16 and miR-21 Levels in Multiple Myeloma: Prognostic Significance of Survival and Response to Lenalidomide Treatment
by Annita-Ioanna Gkioka, Maria Tsota, Aspasia Koudouna, Alexandros Gkiokas, Christina-Aggeliki Mitropoulou, Aikaterini Palaiokrassa, Alexandros Alexandropoulos, Mavra Papadatou-Gigante, Vasiliki Bartzi, Thomais-Marina Tryfou, Petros P. Sfikakis, George V. Dedoussis and Marie-Christine Kyrtsonis
Int. J. Mol. Sci. 2024, 25(11), 6065; https://doi.org/10.3390/ijms25116065 - 31 May 2024
Viewed by 761
Abstract
MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in multiple myeloma (MM) pathogenesis by regulating gene expression. This study evaluated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide–dexamethasone (LD) [...] Read more.
MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in multiple myeloma (MM) pathogenesis by regulating gene expression. This study evaluated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide–dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both correlated with the depth of response and mir-16 with sustained response to LD treatment. Ratios of both miR-16 and miR-21 expression levels (prior to LD treatment/diagnosis) below two predicted a shorter time to response (p = 0.027) and a longer time to next treatment (p = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels correlated with disease variables and treatment outcomes. Full article
(This article belongs to the Special Issue Epigenetics and Immunotherapy in Cancer)
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17 pages, 5842 KiB  
Article
Dynamic Changes in miRNA Expression during the Generation of Expanded and Activated NK Cells
by Chantal Reina-Ortiz, Mª Pilar Mozas, David Ovelleiro, Fei Gao, Martín Villalba and Alberto Anel
Int. J. Mol. Sci. 2023, 24(17), 13556; https://doi.org/10.3390/ijms241713556 - 31 Aug 2023
Viewed by 1582
Abstract
Therapies based on allogenic Natural Killer (NK) cells are becoming increasingly relevant, and our laboratory has produced expanded and activated NK (eNK) cells that are highly cytotoxic against several hematological cancers when used alone or in combination with currently approved therapeutic monoclonal antibodies. [...] Read more.
Therapies based on allogenic Natural Killer (NK) cells are becoming increasingly relevant, and our laboratory has produced expanded and activated NK (eNK) cells that are highly cytotoxic against several hematological cancers when used alone or in combination with currently approved therapeutic monoclonal antibodies. In order to produce eNK cells, healthy human donor NK cells undergo a 20-day expansion protocol with IL-2, IL-15 and Epstein–Barr virus (EBV)-transformed lymphoblastoid feeder cells. In order to produce an even more potent eNK-based therapy, we must elucidate the changes our protocol produces within healthy NK cells. To understand the post-transcriptional changes responsible for the increased cytolytic abilities of eNK cells, we performed microRNA (miRNA) expression analysis on purified NK cells from day 0 and day 20 of the protocol using quantitative reverse transcription PCR (RT-qPCR). Of the 384 miRNAs profiled, we observed changes in the expression of 64 miRNAs, with especially significant changes in 7 of them. The up-regulated miRNAs of note were miRs-146a, -124, -34a, and -10a, which are key in the regulation of cell survival through the modulation of pro-apoptotic genes such as PUMA. The down-regulation of miRs-199a, -223, and -340 was also detected and is associated with the promotion of NK cell cytotoxicity. We validated our analysis using immunoblot and flow cytometry studies on specific downstream targets of both up- and down-regulated miRNAs such as PUMA and Granzyme B. These results corroborate the functional importance of the described miRNA expression patterns and show the wide variety of changes that occur in eNK cells at day 20. Full article
(This article belongs to the Special Issue Epigenetics and Immunotherapy in Cancer)
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Review

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22 pages, 1338 KiB  
Review
γδ T Cells: A Game Changer in the Future of Hepatocellular Carcinoma Immunotherapy
by Stavros P. Papadakos, Konstantinos Arvanitakis, Ioanna E. Stergiou, Maria-Loukia Koutsompina, Georgios Germanidis and Stamatios Theocharis
Int. J. Mol. Sci. 2024, 25(3), 1381; https://doi.org/10.3390/ijms25031381 - 23 Jan 2024
Cited by 3 | Viewed by 2956
Abstract
Hepatocellular carcinoma (HCC) remains a global health challenge with limited treatment options and a poor prognosis for advanced-stage patients. Recent advancements in cancer immunotherapy have generated significant interest in exploring novel approaches to combat HCC. One such approach involves the unique and versatile [...] Read more.
Hepatocellular carcinoma (HCC) remains a global health challenge with limited treatment options and a poor prognosis for advanced-stage patients. Recent advancements in cancer immunotherapy have generated significant interest in exploring novel approaches to combat HCC. One such approach involves the unique and versatile subset of T cells known as γδ T cells. γδ T cells represent a distinct subset of T lymphocytes that differ from conventional αβ T cells in terms of antigen recognition and effector functions. They play a crucial role in immunosurveillance against various malignancies, including HCC. Recent studies have demonstrated that γδ T cells can directly recognize and target HCC cells, making them an attractive candidate for immunotherapy. In this article, we aimed to explore the role exerted by γδ T cells in the context of HCC. We investigate strategies designed to maximize the therapeutic effectiveness of these cells and examine the challenges and opportunities inherent in applying these research findings to clinical practice. The potential to bring about a revolutionary shift in HCC immunotherapy by capitalizing on the unique attributes of γδ T cells offers considerable promise for enhancing patient outcomes, warranting further investigation. Full article
(This article belongs to the Special Issue Epigenetics and Immunotherapy in Cancer)
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17 pages, 846 KiB  
Review
Is Cell-Free DNA Testing in Hepatocellular Carcinoma Ready for Prime Time?
by Sravan Jeepalyam, Ankur Sheel, Aslam Ejaz, Eric Miller and Ashish Manne
Int. J. Mol. Sci. 2023, 24(18), 14231; https://doi.org/10.3390/ijms241814231 - 18 Sep 2023
Cited by 2 | Viewed by 2123
Abstract
Revamping the current biomarker landscape of hepatocellular carcinoma (HCC) with cell-free DNA (cfDNA) could improve overall outcomes. The use of commercially available cfDNA testing (also known as liquid biopsy) is limited by the low prevalence of targetable mutations and does not have any [...] Read more.
Revamping the current biomarker landscape of hepatocellular carcinoma (HCC) with cell-free DNA (cfDNA) could improve overall outcomes. The use of commercially available cfDNA testing (also known as liquid biopsy) is limited by the low prevalence of targetable mutations and does not have any prognostic or predictive value. Thus, current cfDNA testing cannot be relied upon for perioperative risk stratification (POR), including early detection of recurrence, long-term surveillance, predicting outcomes, and treatment response. Prior evidence on cfDNA mutation profiling (non-specific detection or gene panel testing) suggests that it can be a reliable tool for POR and prognostication, but it still requires significant improvements. cfDNA methylation changes or epigenetic markers have not been explored extensively, but early studies have shown potential for it to be a prognostic biomarker tool. The predictive value of cfDNA (mutations and EM) to assist treatment selection (systemic therapy, immune-checkpoint inhibitor vs. tyrosine kinase inhibitor) and to monitor response to systemic and locoregional therapies should be a future area of focus. We highlighted the unmet needs in the HCC management and the current role of cfDNA testing in HCC in addressing them. Full article
(This article belongs to the Special Issue Epigenetics and Immunotherapy in Cancer)
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