SPP1 and Hepatic fibrosis: Previous studies have found SPP1+ macrophages to correlate with poor clinical outcomes in various cancer types.18,38,39 SPP1+ expression in healthy liver has been reported to be minimal and mainly localized to Kupffer cells compared to other immune cells.40 Fibronectin is a critical component of the extracellular matrix in liver fibrosis and has been linked to tumor recurrence after curative treatment.41,42 Given these enriched interactions, the role of SPP1+ and FN1+ macrophages in TAS CD8+ T cell dysfunction was further studied.