Mechanisms of Cancer Cells Escape from Immune Surveillance: The Focus on Epigenetic and Pro-inflammatory Adaptations

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 2463

Special Issue Editors


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Guest Editor
College of Nursing and Health Sciences, Flinders Medical Centre, Flinders University, Adelaide 5001, Australia
Interests: breast cancer; esophageal adenocarcinoma; hepatocellular carcinoma; estrogen receptors; sphingolipids; cancer stem cells; immune evasion; cytokine storm
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Guest Editor
Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Severnii pr-d 1, Chernogolovka 142432, Russia
Interests: brain cancer; glycolysis; abnormal tumor metabolism; tumor biomarkers; apoptosis; chemotherapy; multitarget anticancer agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Anti-cancer surveillance is one of the most important functions of the immune system as it helps to eliminate transformed and malfunctioning cells. However, many cancer cells manage to hide from the screening for elimination and/or survive the immune defense mechanisms. Cancer cell survival results in the development of resistance, metastasis, and cancer recurrence. The development of cancer resistance is a multifactorial and largely unclear process that is orchestrated by various signaling mechanisms, including growth-promoting and anti-apoptotic gene activation. Epigenetic factors and the tumor microenvironment are often involved in the regulation of carcinogenesis and development of chemo- and radiotherapy resistance. Elevated and/or disbalanced levels of pro-inflammatory molecules may often contribute to the development of resistance and promote the cancer progression toward a more aggressive phenotype, which is associated with high cancer morbidity and mortality. This Special Issue of Cancers presents current advances in the understanding of molecular mechanisms of cancer cell escape from immune surveillance and development of cancer chemo- and radio-resistance. The Issue is also focused on the description of novel anticancer methodologies that target epigenetic gene regulation and the pro-inflammatory tumor microenvironment. Original research manuscripts, insightful reviews, and idea-provoking letters that discuss novel mechanisms of cancer cells' adaptations to immune surveillance, survival, and resistance are invited.

Dr. Olga Sukocheva
Dr. Margarita Neganova
Guest Editors

Manuscript Submission Information

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Keywords

  • immune surveillance
  • cancer resistance
  • tumor microenvironment
  • cancer immunoediting
  • epigenetic regulation
  • apoptosis
  • necroptosis
  • cuproptosis

Published Papers (2 papers)

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Research

14 pages, 7348 KiB  
Article
Astragaloside IV Attenuates Programmed Death-Ligand 1-Mediated Immunosuppression during Liver Cancer Development via the miR-135b-5p/CNDP1 Axis
by Yang Ma, Yan Li, Taotao Wu, Yingshuai Li and Qi Wang
Cancers 2023, 15(20), 5048; https://doi.org/10.3390/cancers15205048 - 19 Oct 2023
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Abstract
Background: Astragaloside IV (AS-IV) is a pivotal contributor to anti-tumour effects and has garnered extensive attention in research. Tumour cell immune suppression is closely related to the increase in Programmed Death-Ligand 1 (PD-L1). Hepatocellular carcinoma (HCC) is a malignant tumour originating from hepatic [...] Read more.
Background: Astragaloside IV (AS-IV) is a pivotal contributor to anti-tumour effects and has garnered extensive attention in research. Tumour cell immune suppression is closely related to the increase in Programmed Death-Ligand 1 (PD-L1). Hepatocellular carcinoma (HCC) is a malignant tumour originating from hepatic epithelial tissue, and the role of AS-IV in regulating PD-L1 in anti-HCC activity remains unclear. Methods: Various concentrations of AS-IV were administered to both human liver immortalised cells (THEL2) and HCC (Huh-7 and SMMC-7721), and cell growth was assessed using the CCK-8 assay. HCC levels and cell apoptosis were examined using flow cytometry. Mice were orally administered AS-IV at different concentrations to study its effects on HCC in vivo. Immunohistochemistry was employed to evaluate PD-L1 levels. Western blotting was employed to determine PD-L1 and CNDP1 protein levels. We carried out a qRT-PCR to quantify the levels of miR-135b-3p and CNDP1. Finally, a dual-luciferase reporter assay was employed to validate the direct interaction between miR-135b-3p and the 3′UTR of CNDP1. Results: AS-IV exhibited a dose-dependent inhibition of proliferation in Huh-7 and SMMC-7721 while inhibiting PD-L1 expression induced by interferon-γ (IFN-γ), thus attenuating PD-L1-mediated immune suppression. MiR-135b-5p showed significant amplification in HCC tissues and cells. AS-IV mitigated PD-L1-mediated immune suppression through miR-135b-5p. MiR-135b-5p targeted CNDP1, and AS-IV mitigated PD-L1-induced immunosuppression by modulating the miR-135b-5p/CNDP1 pathway. Conclusion: AS-IV decreases cell surface PD-L1 levels and alleviates PD-L1-associated immune suppression via the miR-135b-5p/CNDP1 pathway. AS-IV may be a novel component for treating HCC. Full article
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23 pages, 3010 KiB  
Article
Hydroxamic Acids Containing a Bicyclic Pinane Backbone as Epigenetic and Metabolic Regulators: Synergizing Agents to Overcome Cisplatin Resistance
by Yulia Aleksandrova, Aldar Munkuev, Evgenii Mozhaitsev, Evgeniy Suslov, Konstantin Volcho, Nariman Salakhutdinov and Margarita Neganova
Cancers 2023, 15(20), 4985; https://doi.org/10.3390/cancers15204985 - 14 Oct 2023
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Abstract
Multidrug resistance is the dominant obstacle to effective chemotherapy for malignant neoplasms. It is well known that neoplastic cells use a wide range of adaptive mechanisms to form and maintain resistance against antitumor agents, which makes it urgent to identify promising therapies to [...] Read more.
Multidrug resistance is the dominant obstacle to effective chemotherapy for malignant neoplasms. It is well known that neoplastic cells use a wide range of adaptive mechanisms to form and maintain resistance against antitumor agents, which makes it urgent to identify promising therapies to solve this problem. Hydroxamic acids are biologically active compounds and in recent years have been actively considered to be potentially promising drugs of various pharmacological applications. In this paper, we synthesized a number of hydroxamic acids containing a p-substituted cinnamic acid core and bearing bicyclic pinane fragments, including derivatives of (−)-myrtenol, (+)-myrtenol and (−)-nopol, as a Cap-group. Among the synthesized compounds, the most promising hydroxamic acid was identified, containing a fragment of (−)-nopol in the Cap group 18c. This compound synergizes with cisplatin to increase its anticancer effect and overcomes cisplatin resistance, which may be associated with the inhibition of histone deacetylase 1 and glycolytic function. Taken together, our results demonstrate that the use of hydroxamic acids with a bicyclic pinane backbone can be considered to be an effective approach to the eradication of tumor cells and overcoming drug resistance in the treatment of malignant neoplasms. Full article
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