SPP1 and neoplasm: TAMs expressing different markers also show differential spatial distribution; for instance, SPP1+macrophages are enriched in hypoxic and necrotic tumor regions, where they promote tumor progression can serve as indicators of poor prognosis (44); TAMs at tumor margin areas express high levels of interleukin 4 induced 1 protein (IL-4I1), which is related to the invasiveness of colon cancer (45); and PD-L1+ macrophages also accumulate at the tumor invasion margin, forming dense cluster-like structures (46).