Scavenger Receptor

Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors characterized by their capacity to remove extraneous or modified self-macromolecules from circulation, thus avoiding the accumulation of noxious agents in the extracellular space. Scavenger receptors (SRs) such as CD5 and SR-B1 constitute macromolecular recognition and signaling platforms that can mediate both anti-inflammatory and pro-inflammatory responses. These activities can be exploited in cancer immunotherapy by modulating their pro/anti-inflammatory activities. Scavenger receptors (SRs) constitute another family of cell surface and soluble PRRs, which encompasses several heterogeneous groups of structurally and/or functionally diverse receptors. 
They were initially reported as endocytic macrophage receptors for modified (e.g., acetylated or oxidized) low-density lipoproteins. Generally speaking, SRs sense and/or endocytose a broad range of endogenous and exogenous noxious ligands. However, they can also subserve other functions such as cell adhesion and antigen presentation. This multifunctional versatility is in part due to their structural diversity. Indeed, SRs are multidomain proteins grouped into several classes (A to J) mainly differing in their extracellular domain composition. Most SRs possess intracytoplasmic regions coupling them to intracellular signaling cascades. In the steady state, this signaling leads to the induction of tolerance and can be considered a major anti-inflammatory pathway. This mechanism has been exploited to induce IL-10-producing suppressive CD4+ T cells targeting self and foreign antigens to DCs via the DC-asialoglycoprotein receptor.
The induction of such suppressive T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. The SRs are often hijacked by pathogens to invade cellular compartments, thus avoiding intracellular degradation mechanisms. This can be exemplified by the scavenger receptor class B type 1 (SR-B1) through which hepatitis c virus and Plasmodium spp. pathogens enter the host cells. Certain SRs can also function as co-receptors, presenting certain ligands to other danger receptors such as TLRs. Thus, SRs can be envisioned as adaptive danger receptors with the ability to induce tolerance or immunity, depending on the presence of MAMPs or DAMPs. Emerging evidence reveals that SRs can play a role as regulators of tumor behavior and host immune responses to tumors. This is illustrated by recent findings on the biology of CD5 and SR-B1, two SRs behaving as putative regulators of tumorigenesis, cancer invasion, and the anti-tumor immune response.


1.Vasquez M,et al. Eur J Immunol. 2017;47(7):1108–1118.