Targeting MARCO in CASH: Balancing Antitumor Immunity and Hepatic Homeostasis

We read with great interest the recent study by Ding et al.1 describing how MARCO+ macrophages mediate an immunosuppressive microenvironment in chemotherapy-associated steatohepatitis (CASH) and drive colorectal liver metastasis. Using single-cell profiling and an irinotecan-induced murine CASH model, the authors report an accumulation of immunosuppressive MARCO+ macrophages accompanied by exhausted CD8+TOX+ T cells and stressed NK cells. They further suggest that MARCO+ macrophages emerge during steatohepatitis and promote metastasis, as deletion of MARCO reduces liver tumor burden and T-cell exhaustion.