Targeting of CD163+ Macrophages in Inflammatory and Malignant Diseases

Abstract

The macrophage is a key cell in the pro- and anti-inflammatory response including that of the inflammatory microenvironment of malignant tumors. Much current drug development in chronic inflammatory diseases and cancer therefore focuses on the macrophage as a target for immunotherapy. However, this strategy is complicated by the pleiotropic phenotype of the macrophage that is highly responsive to its microenvironment. The plasticity leads to numerous types of macrophages with rather different and, to some extent, opposing functionalities, as evident by the existence of macrophages with either stimulating or down-regulating effect on inflammation and tumor growth. The phenotypes are characterized by different surface markers and the present review describes recent progress in drug-targeting of the surface marker CD163 expressed in a subpopulation of macrophages. CD163 is an abundant endocytic receptor for multiple ligands, quantitatively important being the haptoglobin-hemoglobin complex. The microenvironment of inflammation and tumorigenesis is particular rich in CD163+ macrophages. The use of antibodies for directing anti-inflammatory (e.g., glucocorticoids) or tumoricidal (e.g., doxorubicin) drugs to CD163+ macrophages in animal models of inflammation and cancer has demonstrated a high efficacy of the conjugate drugs. This macrophage-targeting approach has a low toxicity profile that may highly improve the therapeutic window of many current drugs and drug candidates.

MSC-like cells increase ability of monocyte-derived dendritic cells to polarize IL-17-/IL-10-producing T cells via CTLA-4

“…This observation suggests that the presentation of lipid and glycolipid antigens by monocyte-derived cells through group 1 CD1 proteins may be negatively modulated by MSCl cells either in a direct or an indirect manner. For further characterization of phenotypic changes of MSCl-CM- and MSCl cell-treated monocyte-derived cells, expression of CD163, a macrophage scavenger receptor ( Skytthe et al., 2020 ), was investigated. Interestingly, treatment with MSCl-CM induced only a slight increase in the frequency of CD163 + cells, whereas exposure to MSCl cells triggered a significant rise in the ratio of the macrophage marker-expressing cells ( Figure S2 A).…”

MALDI MSI Reveals the Spatial Distribution of Protein Markers in Tracheobronchial Lymph Nodes and Lung of Pigs after Respiratory Infection

“…In the present study, we have focused on detecting, identifying, and mapping a typical inflammation marker CD163 [34], and specific interleukins and other infectious markers in cryosections of porcine lung tissue affected by APP. After on-tissue trypsinization, we searched MALDI MSI data for specific peptides of CD163 and different interleukins (IL-1β; IL-6; IL-8).…”

Anti-Tumoral and Anti-Angiogenic Effects of Low-Diluted Phenacetinum on Melanoma

“…Mostly, macrophages were able to polarize in response to inflammatory microenvironment and found themselves involved in many cancers, including melanoma, as an indicator of poor prognosis ( 55 , 56 ). Among subpopulation of macrophages, the surface marker CD163 is usually targeted to identify tumor-associated macrophages (TAMs) ( 57 ). TAMs sense hypoxia in avascular areas of tumors and react in turn by releasing pro-angiogenic factors such as FGF-2, TNF-α, and VEGFs, which again promotes tumor oxygenation by the direct recruitment of endothelial cells ( 58 , 59 ).…”