Figure 2.

Schematic representation of the potential tumor location and tumor microenvironment (TME) in H&N cancer. (A) H&N cancer may be found at oral, nasal, and paranasal cavities, larynx, and pharynx anatomical sites. (B) Clinical image of stage 2 tongue cancer (<4 cm) provided by Drs. Yo Kishimoto and Hideaki Okuyama’s research team at the Kyoto University Hospital with patient’s consent. (C) Heterogeneous cell populations are resided within an H&N squamous cell carcinoma. Stromal cells including mesenchymal stem cells and fibroblasts are commonly found in the outer layer of the tumorous body. Tumor-infiltrating immune cells including macrophages and T cells among others are found within the tumor. (D) The extracellular matrix provides structural support and biochemical cues to the TME via cell–cell/–ECM interactions. Mutation of pathways PI3K/Akt/mTOR, TP53, NOTCH, EGFR, JAK/STAT, Ras/MEK/ERK, and MET relate to H&N cancer development. (E) The hypoxic region is located at the center of the tumor, which is characterized by aberrant vasculature. (F) This fenestrated vasculature hampers the proper supply of nutrients, oxygen, and therapeutics. ECM, extracellular matrix; IL, interleukin; MDSC, myeloid-derived suppressor cell; MMP, metalloproteinase; VEGF, vascular epithelial growth factor. Figure created with BioRender.com.