Molecular cancer, 2021-12, Vol.20 (1), p.171-171, Article 171
2021
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- Autor(en) / Beteiligte
- Titel
- Epigenetic modulation of antitumor immunity for improved cancer immunotherapy
- Ist Teil von
- Molecular cancer, 2021-12, Vol.20 (1), p.171-171, Article 171
- Ort / Verlag
- England: BioMed Central Ltd
- Erscheinungsjahr
- 2021
- Quelle
- SpringerLink
- Beschreibungen/Notizen
- Epigenetic mechanisms play vital roles not only in cancer initiation and progression, but also in the activation, differentiation and effector function(s) of immune cells. In this review, we summarize current literature related to epigenomic dynamics in immune cells impacting immune cell fate and functionality, and the immunogenicity of cancer cells. Some important immune-associated genes, such as granzyme B, IFN-γ, IL-2, IL-12, FoxP3 and STING, are regulated via epigenetic mechanisms in immune or/and cancer cells, as are immune checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) expressed by immune cells and tumor-associated stromal cells. Thus, therapeutic strategies implementing epigenetic modulating drugs are expected to significantly impact the tumor microenvironment (TME) by promoting transcriptional and metabolic reprogramming in local immune cell populations, resulting in inhibition of immunosuppressive cells (MDSCs and Treg) and the activation of anti-tumor T effector cells, professional antigen presenting cells (APC), as well as cancer cells which can serve as non-professional APC. In the latter instance, epigenetic modulating agents may coordinately promote tumor immunogenicity by inducing de novo expression of transcriptionally repressed tumor-associated antigens, increasing expression of neoantigens and MHC processing/presentation machinery, and activating tumor immunogenic cell death (ICD). ICD provides a rich source of immunogens for anti-tumor T cell cross-priming and sensitizing cancer cells to interventional immunotherapy. In this way, epigenetic modulators may be envisioned as effective components in combination immunotherapy approaches capable of mediating superior therapeutic efficacy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1476-4598eISSN: 1476-4598DOI: 10.1186/s12943-021-01464-xTitel-ID: cdi_doaj_primary_oai_doaj_org_article_ac9a3006188a44c59d2611abef281c60
- Format
- –
- Schlagworte
- Adenomatous polyposis coli, Animals, Antigen (tumor-associated), Antigen presentation, Antigen processing, Antigen-presenting cells, Antigens, Antineoplastic Agents, Immunological - pharmacology, Antineoplastic Agents, Immunological - therapeutic use, Biomarkers, Tumor, Cancer, Cancer immunotherapy, Cancer therapies, Care and treatment, CD223 antigen, Cell death, Cell fate, Clinical Trials as Topic, Combined Modality Therapy, CTLA-4 protein, Cytoplasm, Development and progression, Disease Management, Disease Susceptibility, DNA methylation, Drug Development, Effector cells, Energy Metabolism, Enzymes, Epigenesis, Genetic, Epigenetic inheritance, Epigenetic reprogramming, Epigenetics, Foxp3 protein, Gene Expression Regulation, Neoplastic, Genes, Genomes, Granzyme B, Health aspects, Heterogeneity, Histone modifications, Humans, Immune cells, Immune response, Immunity, Immunogenicity, Immunomodulation, Immunomodulation - genetics, Immunosuppressive agents, Immunotherapy, Immunotherapy - methods, Interleukin 12, Interleukin 2, Kinases, Localization, Lymphocytes, Lymphocytes T, Major histocompatibility complex, Mammals, Metabolic reprogramming, Metastasis, Methylation, Neoantigens, Neoplasms - etiology, Neoplasms - metabolism, Neoplasms - therapy, PD-1 protein, Phosphorylation, Proteins, Review, Signal Transduction - drug effects, Stromal cells, T cells, Transcription, Treatment Outcome, Tumor Microenvironment - drug effects, Tumor Microenvironment - genetics, Tumor Microenvironment - immunology, Tumorigenesis, γ-Interferon