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. 2021 Jan 12;6:12. doi: 10.1038/s41392-020-00419-w

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Head and neck squamous cell carcinoma (HNSCC) TME is a complex ecosystem. HNSCC TME is a complex ecosystem consisting of a fabricated network of tumor cells surrounded by non-tumor cells, including cancer-associated fibroblasts (CAFs), endothelial cells (EC), adipocytes, neuroendocrine cells, blood and lymphatic vascular cells, muscle cells, infiltrating immune cells ((T cells, B cells, natural killer cells (NK cells), neutrophils, dendritic cells (DC), Langerhans cells (LCs), macrophages, and myeloid-derived suppressor cells (MDSCs)]. In addition, stromal components, including extracellular matrix (ECM) proteins (collagen, fibronectin, elastin, laminin, and tenascin), intermediate metabolites, nutrients, hormones, growth factors, etc. are the crucial components of HNSCC TME. The complex cross talk between the tumor and the stromal components regulates cell growth, epithelial–mesenchymal transition (EMT), invasion and metastasis, anoikis resistance, angiogenesis, metastatic niche, immune surveillance, and therapeutic resistance making HNSCC tumors very aggressive