Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease

The impact of the lung environment on macrophage development, activation and function: diversity in the face of adversity

“…For instance, while macrophages have historically been described as M1 (“classically-activated”) or M2 (“alternatively-activated”) largely based on in vitro culture systems 1 , it is now beyond doubt that a binary classification such as this is inadequate to capture the complexity of macrophage plasticity and activation states, particularly in vivo 2 . Technological advances have revealed tremendous diversity and heterogeneity between macrophages from different tissues and even within different niches of the same tissue in terms of phenotype, transcriptome and metabolome 3 , 4 . While macrophages generally excel at the ‘silent’ clearance of debris, apoptotic host cells and the capture and destruction of microbial intruders, it is now clear they also play far broader roles and are exquisitely tailored to meet the demands of the local tissue microenvironment in which they reside.…”

NK Cell Anti-Tumor Surveillance in a Myeloid Cell-Shaped Environment

“…Nevertheless, this is an over-simplification due to the variety of phenotypes displayed by these myeloid cells that do not often fit the M1/M2 dichotomous phenotypes. Recent single-cell transcriptomic studies show accumulation of several mononuclear phagocyte (MNP) populations in human tumors, some of which with newly described phenotypes related to prevalent pro-tumor activity (36)(37)(38)(39). Zang and co-workers identified C1QC + and SPP1 + TAM accumulation in colorectal cancer, two populations that differ in phenotypic features related to prevalent proangiogenic and immunosuppressive function, respectively (12).…”

“…Zang and co-workers identified C1QC + and SPP1 + TAM accumulation in colorectal cancer, two populations that differ in phenotypic features related to prevalent proangiogenic and immunosuppressive function, respectively (12). By integrating human monocytes and macrophages (MoMac) single-cell RNA obtained from 41 datasets (the MoMac-VERSE), Mulder et al found that several cancer types display expansion of conserved TAM populations, including IL4I1 + PD-L1 + IDO1 + and TREM2 + that expressed mostly M1 and M2 relate genes, respectively (38).…”

“…Also location of TAMs in the tumor microenvironment (TME) has been correlated with specific functions, with pathogenic macrophages accumulating at the invasive margin in colorectal cancer, and to negatively correlate with T and NK cell infiltration in several cancer types (36,38,39).…”

“…TGF-b is a highly pleiotropic cytokine whose role in physiology and pathological condition is strictly context-dependent; above all activities, TGF-b is a master regulator of the immune response and exerts a predominant inhibitory effect on a variety of immune cells. According to the analysis of the mononuclear phagocyte single cell RNA compendium from 41 datasets (MNP-VERSE), TGF-beta, CD48, Dectin-1 and MS4A4a are equally expressed by all DC subsets found in several human cancer types, i.e progenitor DC (pre-DC), cDC1 and CD11c + cDC2 (that include cDC2 and DC3, DC2/DC3) [Figure 2, (38)]. Cytokines of the TGF-b family represent an important regulatory pathway of activated DCs (72); Activin A, a TGF-b family member, is one of the most upregulated cytokines during NK-DC interaction that was found to act as an important negative feedback mechanism for both NK cell and DC activation (69,73).…”