Further Understanding of the Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: Implications for Prognosis

Abstract

We aimed to review the literature on the tumor microenvironment as a key player in tumor growth and anti-cancer treatment responses in head and neck cancer. Patients and Methods: We reviewed the recent literature on this topic, using the following research words: "tumor microenvironment" and "head and neck cancer or neoplasm or head and neck squamous cell carcinoma" and "immune cells" and "stromal cells". A search was conducted on the PubMed website and reports from international meetings, presentations and abstracts. Results: The tumor microenvironment is a complex network in which myeloid cells, tumoral cells, growth factors and cytokines are involved in angiogenesis, the extracellular matrix and epithelial-to-mesenchymal transition. Conclusion: Immune resistance and rapid tumor growth depend on immunosuppressive and pro-tumoral environments. Further investigations to classify and adequately treat patients with head and neck cancer are required.

Alcohol and Head and Neck Cancer: Updates on the Role of Oxidative Stress, Genetic, Epigenetics, Oral Microbiota, Antioxidants, and Alkylating Agents

“…Since the relationship between alcohol and HNC has been largely established, long-term markers of alcohol consumption, especially those detected in the hair, can give crucial information on the real alcohol drinking habits of HNC patients [ 63 , 64 ]. Furthermore, many prognostic markers related to alcoholism, especially those linked to the polymorphisms of ethanol metabolic pathway components, have been suggested for the detection and monitoring of HNC [ 109 ]. With this knowledge on the etiopathogenesis of HNC and its relation to alcohol-induced oxidative stress and genetic-epigenetic alterations, more attention could be focused on the role of polyphenols and alkylating agents for patient management, especially in the case of heavy drinkers [ 188 , 279 , 287 ].…”

“…Recently, the importance of the tumor microenvironment (TME) [ 105 , 106 , 107 , 108 ] has been emphasized, namely the result of factors associated with cancer, patient’s characteristics (such as oral cavity microbiota, see paragraph below), immune system, and factors related to geographic origin, specifically embodied by the complex and dynamic interactions among the various cells as well as the balance of proangiogenic factors, tissue pH, growth factors, and cytokine production changes over time [ 109 , 110 ]. Typically, HNC-TME is characterized by hypoxia (related to poor prognosis and resistance to radiation therapy) and immune cells infiltration, while an active tumor–stromal cross-talk is essential to promote cancer growth and invasion, with an important role played by cancer-associated fibroblasts (CAFs), chemokines, cytokines, and proliferative and inflammatory signal pathways [ 111 , 112 , 113 ].…”

METTL3 is a Potential Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma

“…In the present study, KEGG pathway analysis indicated that METTL3-related differentially expressed genes were involved not only in common oncogenic pathways but also in immune pathways. Several studies have con rmed the characterization of the immune microenvironment involved in the occurrence and development of HNSCC [34][35][36][37]. Studies have shown that the risk score composed of the m 6 A gene is related to the in ltration of dendritic cells, neutrophils, CD4 + T cells, CD8 + T cells, and B cells, and upregulated m 6 A regulators are positively correlated with PD-L1 in the HNSCC tumor immune microenvironment [38].…”

Understanding the tumor microenvironment in head and neck squamous cell carcinoma

“…Cancer‐associated fibroblasts (CAFs) are activated fibroblasts within the TME. 22 Fibroblast activation protein‐alpha (FAP‐α) and alpha‐smooth muscle chain (α‐SMA) are specific markers to purify CAFs. 23 CAFs play a critical role in tumor evolution by producing collagen fibrils in the extracellular matrix (ECM), eventually increasing invasiveness of HNSCC tumor cells.…”

“…Having been formed, Tregs produce transforming growth factor beta (TGF‐β), IL‐10 and adenosine, thereby suppressing T cells (helper and cytotoxic). 22 MDSCs can also suppress CD8 + T cells by secreting prostaglandin E2 (PGE2) and arginase (ARG). MDSCs were found to be related to a tolerogenic tumor immune landscape.…”