New study, in Immunity, led by researchers from the Peter van Endert group uncovers an unexpected immune function for a rare macrophage population in the spleen.

François-Xavier Mauvais et al. from the Peter van Endert group has revealed that metallophilic marginal zone macrophages (MMMs) — a little-studied population of macrophages located at the frontier of the splenic marginal zone — can do much more than capture pathogens and cellular debris. In this study, the team shows that these macrophages have the remarkable ability to directly activate CD8+ T cells and trigger protective immune responses against tumors.

Using a newly developed purification protocol and advanced imaging techniques, the researchers succeeded in isolating MMMs in unprecedented purity. Their analyses revealed that MMMs express a unique gene signature enabling them to process and present antigens via MHC class I, a molecular pathway usually attributed to dendritic cells. Surprisingly, MMMs can cross-present antigens and stimulate cytotoxic T cells independently of conventional dendritic cells (cDC1s) — challenging a long-standing view in immunology.

The study also highlights the importance of the Batf3 transcription factor, which is required for MMMs to perform this function in vivo. Through a series of tumor models, the team demonstrates that MMMs can induce robust antitumor immunity, both by capturing blood-borne tumor antigens and by internalizing tumor cells seeding the spleen.

These findings redefine the immunological role of MMMs and suggest they may represent a novel cellular target in cancer immunotherapy.

Read the full study here: https://www.cell.com/immunity/abstract/S1074-7613(25)00094-9