Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma

Abstract

The tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC) is comprised of cancer-associated fibroblasts (CAFs), immune cells, and other supporting cells. Genetic changes in the carcinoma cells, such as alterations to TP53, NOTCH1, and specific gene expression profiles, contribute to derangements in cancer and microenvironment cells such as increased ROS, overproduction of cytokines, and epithelial to mesenchymal transition (EMT). CAFs are among the most critical elements of the TME contributing to proliferation, invasion, and metastasis. The adaptive immune response is suppressed in HNSCC through overexpression of cytokines, triggered apoptosis of T cells, and alterations in antigen processing machinery. Overexpression of critical cytokines, such as transforming growth factor-β (TGF-β), contributes to EMT, immune suppression, and evolution of CAFs. Inflammation and hypoxia are driving forces in angiogenesis and altered metabolism. HNSCC utilizes glycolytic and oxidative metabolism to fuel tumorigenesis via coupled mechanisms between cancer cell regions and cells of the TME. Increased understanding of the TME in HNSCC illustrates that the long-held notion of "condemned mucosa" reflects a process that extends beyond the epithelial cells to the entire tissue comprised of each of these elements.

Overexpression of EGFR in Oral Premalignant Lesions and OSCC and Its Impact on Survival and Recurrence

“…A study utilized next-generation sequencing and identified EGFR as one of the most commonly mutated cancer-related gene in OSCC [31] and it is also considered a major player in oral carcinogenesis [32] as it was found to harbour genetic alterations as a result of repeated exposure to risk factors [19]. According to Gupta et al, EGFR overexpression lead to lower overall survival, overall response and quality of life in patients with locally advanced OSCC who had been treated with chemoradiation [33].…”

Secretome profiling of oral squamous cell carcinoma-associated fibroblasts reveals organization and disassembly of extracellular matrix and collagen metabolic process signatures

“…There is evidence that all components of the tumor stroma can critically influence carcinogenesis and the malignant phenotype in multiple stages of tumor development [5,6]. Among these components, CAFs, fibroblast-like cells that acquire the ability to express isoform α of the smooth muscle actin (α-SMA) and synthesize an extensive repertoire of cytokines, growth factors, chemokines, hormones, neurotransmitters, inflammatory mediators, adhesion proteins, and most abundantly extracellular matrix proteins, have been highlighted as the major player in tumor-stroma cross talk [7].…”

Tumor Microenvironment in Head and Neck Squamous Cell Carcinomas

“…Though it is considered that inflammation creates a beneficial effect in the removal of pathological structures and in the destruction of cancer cells, inflammatory response that is unorganized and managed by the cancer cells creates an opportunity for the development of the tumor and for the cancer cells to evade the devastating effects of the immune system. Research conducted in head and neck cancers have clearly revealed that local, regional, and systemic inflammatory responses are dysfunctional (16,17).…”

“…Undergoing myofibroblastic changes, these cells have a phenotype characterized by dense ultrastructural α-smooth muscle actin deposition. In addition, integrin α6 overexpression, which is important in cell adhesion and surface signaling, is also determined (17).…”