Macrophage diversity in cancer revisited in the era of single-cell omics

Tumor-associated macrophages (TAMs) have multiple potent functions in cancer and, thus, represent important therapeutic targets. These diverse functions highlight the heterogenous nature of TAMs. Recent single cell omics technologies have significantly advanced our understanding of the molecular diversity of TAMs. However, a unifying nomenclature of TAM diversity and annotation of their molecular signatures is lacking. Here, we review recent major studies of single cell transcriptome, epigenome, metabolome, and spatial omics of cancer with a specific focus on TAMs. We also propose a consensus model of TAM diversity and present avenues for future research. TAMs have diverse functions in cancer, reflecting the heterogenous nature of these immune cells. Here, we propose a new nomenclature to identify TAM subsets.Recent single cell multi-omics technologies, which allow the clustering of TAM subsets in an unbiased manner, have significantly advanced our understanding of the molecular diversity of TAMs in mice and humans.Novel mechanisms and potential therapeutic targets have been identified that might regulate the tumor-promoting function of different TAM subsets.TAM diversity opens promising therapeutic opportunities for envisaging putative cancer treatments.