Tumor microenvironment in head and neck squamous cell carcinoma.
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.
Department of Otolaryngology Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA. Electronic address: joseph.curry@jefferson.edu.
Joseph M
JM
Curry
Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA.
John
J
Sprandio
Department of Otolaryngology Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA.
David
D
Cognetti
Department of Otolaryngology Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA.
Adam
A
Luginbuhl
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA.
Voichita
V
Bar-ad
Department of Otolaryngology Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA.
Edmund
E
Pribitkin
Department of Pathology, Thomas Jefferson University, Philadelphia, PA.
Madalina
M
Tuluc
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology; D001485:Basement Membrane / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007107:Immune System; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism; D017382:Reactive Oxygen Species; D017154:Stromal Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000378:metabolism; D059016:Tumor Microenvironment
D016207:Cytokines; D017382:Reactive Oxygen Species; D020782:Matrix Metalloproteinases