Epigenetic editing and tumor‑dependent immunosuppressive signaling in head and neck malignancies (Review)

Abstract

Head and neck cancer (HNC) comprises a heterogeneous variety of malignant tumors, characterized by a relatively high tumor mutation burden. Previous data have revealed that immune system dysfunction appears to serve a key role in the development and progression of HNC and established immunosuppression is vital for evading the host immune response. Despite progress in chemotherapy and radiotherapy, the survival rate of patients with HNC is still low. Therefore, the present review discusses the development of novel immunotherapy approaches based on the various immune cell signaling routes that trigger drug resistance and immunosuppression. Additionally, the present review discusses the epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling and non-coding RNAs that drive and support HNC progression. Furthermore, the role of cancer-associated fibroblasts, tumor macrophages and myeloid cells in tumor-related immunosuppression are considered. Specifically, the molecular immune-related mechanisms in the tumor microenvironment, which lead to decreased drug sensitivity and tumor relapse, and strategies for reversing drug resistance and targeting immunosuppressive tumor networks are discussed. Deciphering these molecular mechanisms is essential for preclinical and clinical investigations in order to enhance therapeutic efficacy. Furthermore, an improved understanding of these immune cell signaling pathways that drive immune surveillance, immune-driven inflammation and tumor-related immunosuppression is necessary for future personalized HNC-based therapeutic approaches. Contents1. Introduction 2. Current immunotherapy regimens 3. Impact of DNA methylation on disease pathogenesis 4. Regulation via histone modifications 5. Chromatin remodeling as a driver of cancer 6. Molecular role of lncRNAs 7. Circular RNAs (circRNAs) in HNC progression 8. CAFs in the tumor microenvironment 9. Myeloid-derived suppressor cell (MDSC)-related immunosuppression 10. Crosstalk with TAMs 11. Conclusions

Molecular pathways and targeted therapies in head and neck cancers pathogenesis

“…For example, MIR31HG lncRNA appears to promote HIF1A and P21 expression, inducing proliferation and tumorigenesis, and LINC00460 lncRNA promotes the proliferation of HNSCC cells and epithelial-mesenchymal transition-mediated metastasis. On the other hand, SLC26A4-AS1 lncRNA interferes with cell invasiveness, migration, and metastasis, with a tumor suppressor role ( 207 )…”

Biological mechanisms underlying depression, epigenetics and their interplay (Review)

“…Epigenetics, i.e., heritable and stable structural and biochemical alterations of the chromosome that are not associated with DNA sequence alterations, have been associated with numerous physiological and pathological processes, such as metabolic disorders, autoimmune diseases, cancer and neuropsychiatric disorders (44)(45)(46)(47)(48)(49)(50). Epigenetic mechanisms include DNA methylation, regulation by non-coding RNAs (ncRNAs) and histone modifications (Fig.…”

Nucleolin‑based targeting strategies in cancer treatment: Focus on cancer immunotherapy (Review)

“…Epigenetic regulation is well known for its effect on protein expression, which contributes to cancer initiation and progression, including DNA methylation, histone modification, nucleosome remodeling and RNA or microRNA-mediated targeting molecules (36,37). The epigenetic regulators are targetable and have become prognostic biomarkers for various types of cancers including brain, breast, liver, ovary, prostate, gastric, lung, colorectal cancers, melanoma and angiosarcoma (36)(37)(38)(39). NCL was also identified as an epigenetic regulator of leukemogenesis (40).…”