Fig. 4.

By directly inhibiting the activation of stellate cells and cancer-associated fibroblasts (CAFs), halofuginone (HF) can reduce the deposition of collagen, hyaluronic acid, and prolyl 4-hydroxylase A, which are extracellular matrix (ECM) components that limit drug resistance pathways, improve the attractiveness of immune cells to cancer cell signals, augment drug release, and move along the ECM to access tumors. HF treatment blocked the collagen network in tumors by modulating the immunosuppressive tumor microenvironment (TME), enriching the tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), and promoting Treg infiltration. MDSCs: myeloid-derived suppressor cells.