Desmoplastic reaction in the microenvironment of head and neck and other solid tumors: the therapeutic barrier

Area of Science:

• Oncology
• Cancer Biology
• Tumor Microenvironment Research

Background:

• Head and neck squamous cell carcinoma (HNSCC) presents significant challenges due to a lack of effective prognostic biomarkers and therapies.
• The tumor microenvironment (TME), specifically the desmoplastic reaction (DR) involving stromal fibrosis, is increasingly recognized for its role in HNSCC progression and therapeutic resistance.

Purpose of the Study:

• To review the biological significance of the desmoplastic reaction (DR) in the initiation, progression, and treatment resistance of HNSCC.
• To explore the impact of DR on clinical outcomes, immune responses, and therapeutic strategies in HNSCC.

Main Methods:

• Literature review synthesizing existing research on the desmoplastic reaction in HNSCC.
• Analysis of histological correlations between DR, invasion patterns, and patient survival.
• Examination of the role of cancer-associated fibroblasts (CAFs) and extracellular matrix remodeling in DR-mediated effects.

Main Results:

• DR in HNSCC is linked to specific invasion patterns and negatively impacts disease-free and overall survival.
• CAFs within the TME contribute to immune evasion and resistance to immunotherapy.
• DR influences epithelial-mesenchymal transition, bone invasion, and chemotherapy resistance via CAF signaling pathways.

Conclusions:

• The desmoplastic reaction is a critical factor in HNSCC progression and resistance to various therapies, including immunotherapy.
• Distinct DR characteristics in human papillomavirus-driven HNSCC influence prognosis.
• Targeting DR and stromal interactions presents a viable strategy to enhance therapeutic efficacy in HNSCC.