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.
ABSTRACT
H uman papillomavirus (HPV) is considered the main cause of the increasing incidence rates of oropharyngeal squamous cell carcinoma (OPSCC), and soon, the global burden of HPV-related OPSCC is predicted to exceed that of cervical cancer. Moreover, a different molecular profile for HPV-related OPSCC has been described, opening new promising targeted therapies and immunotherapy approaches. Epigenetic and microbiome-based exploration of biomarkers has gained growing interest with a view to the primary oropharyngeal cancer (OPC) screening. Understanding the role of the epigenetic mechanism and the changes that occur during pathogenesis shows appreciable progress in recent years. The different methylation status of DNA and miRNAs demonstrates the value of possible biomarkers discriminating even in different stages of dysplasia. Through whole-genome bisulfite sequencing, differentially methylated regions (DMRs) hold the key to recover missing information. O n the other hand, the microbiota investigation signifies a new biomarker approach for the evaluation of OPC. Along with known cofactors playing a major role in microbiota differentiation, HPV-related cases must be explored further for better understanding. The dynamic approach of the shotgun metagenomic sequencing will robustly fill the gap especially in species/strain level and consequently to biomarker detection. The constantly growing incidence of HPV-related OPC should lead us in further investigation and understanding of the unique features of the disease, more accurate diagnostic methods, along with the development and implementation of new, targeted therapies. This paper comprehensively reviews the significance of biomarkers based on epigenetics and microbiome profile in the accuracy of the diagnosis of the HPV-related cancer in the oropharynx.
