MARCO is a pattern recognition receptor expressed predominantly in tissue macrophages, particularly in the lung, liver, and lymph nodes. It contains a characteristic collagenous domain and functions as a bacteria-binding receptor that recognizes both Gram-positive and Gram-negative bacteria 1, playing a key role in innate immune recognition of unopsonized particles. The receptor localizes to the plasma membrane and mediates phagocytosis and receptor-mediated endocytosis of bacterial pathogens. The bacteria-binding region maps to the cysteine-rich C-terminal domain 1, and MARCO also binds the secretoglycoprotein SCGB3A2. Expression of MARCO is dynamically regulated during infection and inflammatory conditions; peripheral blood mononuclear cells from patients who developed reactive arthritis after Salmonella infection expressed MARCO, whereas those who recovered without sequelae did not 2. In glioblastomas, MARCO marks a pro-tumor macrophage subset associated with worse prognosis and mesenchymal subtype, and its expression changes in response to anti-PD1 checkpoint inhibitors 3. Similarly, in intrahepatic cholangiocarcinoma, MARCO+ tumor-associated macrophages co-localize with cathepsin E-expressing tumor cells to create an immune-resistant microenvironment linked to the poorest survival outcomes 4. These findings identify MARCO-expressing macrophages as potential therapeutic targets in cancer immunotherapy.