SPP1 and neoplasm: In support of this, liver metastases were shown to be enriched with SPP1+ and MRC1+CCL18+ macrophages (IHC confirmed), which exhibit a M2-polarized phenotype with high expression of anti-inflammatory and pro-M2 conversion genes (APOE and MARCO) and a metabolic shift toward amino acid metabolism, a process tightly linked to tumor outgrowth, metastasis and therapeutic resistance through tight regulation of immune cell activity (Wu et al., 2022; Yang et al., 2023).