The pathological features of pulmonary fibrosis (PF) are the abnormal activation and proliferation of myofibroblasts and the extraordinary deposition of the extracellular matrix (ECM). However, the pathogenesis of PF is still indistinct. In recent years, many researchers have realized that endothelial cells had a crucial role in the development of PF. Studies have demonstrated that about 16% of the fibroblasts in the lung tissue of fibrotic mice were derived from endothelial cells. Endothelial cells transdifferentiated into mesenchymal cells via the endothelial–mesenchymal transition (E(nd)MT), leading to the excessive proliferation of endothelial-derived mesenchymal cells and the accumulation of fibroblasts and ECM. This suggested that endothelial cells, a significant component of the vascular barrier, played an essential role in PF. Herein, this review discusses E(nd)MT and its contribution to the activation of other cells in PF, which could provide new ideas for further understanding the source and activation mechanism of fibroblasts and the pathogenesis of PF.

Hepatocellular carcinoma (HCC) arises predominantly in chronic liver disease with a uniquely tolerogenic microenvironment. Immune checkpoint inhibitors (ICIs) have improved the prognosis of advanced HCC, yet most patients exhibit low response rates or therapeutic resistance due to the highly immunosuppressive tumor microenvironment. Metabolic reprogramming is not only a core hallmark of HCC but also a key regulatory axis connecting tumor cells and the immune system. HCC cells exhibit pronounced Warburg glycolysis, upregulated glutaminolysis, aberrant lipid storage and oxidation, enhanced ketone metabolism, and altered polyamine flux. These metabolic alterations lead to nutrient competition, lactate accumulation, amino acid depletion, and oncometabolite signaling, resulting in T cell exhaustion, macrophage polarization, T cell expansion, and impaired dendritic cell function, thereby influencing tumor progression, immune escape, and therapeutic resistance. Targeting metabolic–immune crosstalk represents a promising strategy for reversing immunosuppression and enhancing the efficacy of immunotherapy. In this review, we systematically summarize the core patterns of metabolic reprogramming in HCC, dissect the molecular mechanisms of metabolic crosstalk at the tumor–immune interface, and discuss the role of immunometabolic remodeling in therapeutic resistance. This review aims to provide a comprehensive theoretical basis and new research directions for improving the efficacy of HCC treatment by targeting the metabolic–immune regulatory axis.