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. Here, SPP1 is linked to neoplasm.