Fibroblasts and macrophages: Key players in the head and neck cancer microenvironment

Tumor microenvironment comprises tumor cells, various stromal cells, such as carcinoma-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), pericytes, endothelial cells, soluble factors, and extracellular matrix proteins. Tumor-stroma interactions facilitate the progression of head and neck squamous cell carcinoma (HNSCC) in several aspects. HNSCC cells are able to induce normal fibroblasts and macrophages to become CAFs and TAMs, respectively. CAFs can promote HNSCC progression through direct contact and/or paracrine signaling. Such interactions increase the levels of various growth factors, cytokines, chemokines, matrix metalloproteinases, and periostin. TAMs in HNSCC upregulate the production of IL-β, IL-10, and MIP-3α/CCL20, which are involved in tumorigenic processes.313