In this study, we examined mononuclear phagocytes (MNPs), including dendritic cells, monocytes, and macrophages, which have vital functions such as antimicrobial activity, homeostasis, and immune regulation. We integrated 178,651 MNPs from 13 tissues across 41 datasets to create the MNP-VERSE, a comprehensive single-cell RNA compendium for mapping MNPs and identifying conserved gene signatures. We then focused on macrophages and created a MoMac-centered compendium, revealing specialized subsets of macrophages spread across various tissues. Certain subsets were found to be more prevalent in cancer and inflammation. Tumor-associated macrophage populations were conserved across all neoplastic tissues, with a particular focus on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated at the tumor's edge in a T cell-dependent manner. These macrophages matured through interferon-γ and CD40/CD40L signaling and exhibited immunosuppressive characteristics via tryptophan degradation, promoting regulatory T cell entry into tumors. This comprehensive analysis provides a publicly available platform for annotating and analyzing macrophage functions in both healthy and disease states.
DOI: 10.1016/j.immuni.2021.07.007
