The role of fibronectin in the tumor microenvironment - implications for immunotherapy

Contemporary models of tumor progression highlight the key role of the tumor microenvironment (TME) and the extracellular matrix (ECM) in regulating angiogenesis, metastasis, and immune resistance. Among ECM components, oncofetal fibronectin (FN) isoforms containing the EDA and EDB domains are of particular interest because they are highly expressed in solid tumors but absent from normal adult tissues. This review article synthesizes current data on the pathophysiological functions of FN variants in oncogenesis. Particular attention was paid to their role in pathological vascular remodeling, the induction of epithelial-mesenchymal transition (EMT), the formation of pre-metastatic niches, and the generation of an immunosuppressive environment. The study also critically assesses the clinical significance of FN as a biomarker and a potential target for new therapies in breast cancer, ovarian cancer and glioblastoma. The prospects for the use of innovative stromal strategies - including antibody-drug conjugates (ADCs) and immunocytokines - to overcome resistance to standard immunotherapy are also highlighted.