Cancer-associated fibroblasts: Mediators of head and neck tumor microenvironment remodeling

Cancer-associated fibroblasts (CAFs) are involved in critical aspects of head and neck squamous cell carcinoma (HNSCC) pathogenesis, such as the formation of a tumor-permissive extracellular matrix structure, angiogenesis, or immune and metabolic reprogramming of the tumor microenvironment (TME), with implications for metastasis and resistance to radiotherapy and chemotherapy. The pleiotropic effect of CAFs in TME is likely to reflect the heterogeneity and plasticity of their population, with context-dependent effects on carcinogenesis. The specific properties of CAFs provide many targetable molecules that could play an important role in the future therapy of HNSCC. In this review article, we will focus on the role of CAFs in the TME of HNSCC tumors. We will also discuss clinically relevant agents targeting CAFs, their signals, and signaling pathways, which are activated by CAFs in cancer cells, with the potential for repurposing for HNSCC therapy.

Automated summary

Cancer-associated fibroblasts (CAFs) play crucial roles in the pathogenesis of head and neck squamous cell carcinoma (HNSCC), including extracellular matrix structure formation, angiogenesis, immune and metabolic reprogramming in the tumor microenvironment, which contribute to metastasis and resistance to radiotherapy and chemotherapy. The heterogeneity and plasticity of CAFs result in context-dependent effects on carcinogenesis. Targeting specific molecules in CAFs may hold promise for future HNSCC therapy. This review article focuses on the role of CAFs in the HNSCC tumor microenvironment and discusses clinically relevant agents and signaling pathways that can be targeted for therapy.