SPP1 and hepatocellular carcinoma: Compression of peripheral blood vessels by increasing fibrous tissues in the HCC TME creates a local hypoxic microenvironment that promotes SPP1 expression, whereas SPP1+ macrophages interact with CAFs to stimulate extracellular mesenchymal remodeling and promote the formation of tumor immune barrier (TIB) structures, thereby limiting immune infiltration in the core of tumors82.