CD157: From immunoregulatory protein to potential therapeutic target

Abstract

CD157/BST1 glycosylphosphatidylinositol-anchored glycoprotein is an evolutionary conserved dual-function receptor and β-NAD+-metabolizing ectoenzyme of the ADP-ribosyl cyclases gene family. Identified as bone marrow stromal cell and myeloid cell differentiation antigen, CD157 turned out to have a wider expression than originally assumed. The functional significance of human CD157 as an enzyme remains unclear, while it was well established in mouse models. Conversely, the receptor role of CD157 has been clearly delineated. In physiological conditions, CD157 is a key player in regulating leukocyte adhesion, migration and diapedesis. Underlying these functional roles is the ability of CD157 to bind with high affinity selected extracellular matrix components within their heparin-binding domains. CD157 binding to extracellular matrix promotes its interaction with β1 and β2-integrins and induces the organization of a multimolecular complex that is instrumental to the delivery of synergistic outside-in signals leading to optimal cell adhesion and migration, both in physiological and in pathological situations. CD157 also regulates cell adhesion and migration and is a marker of adverse prognosis in epithelial ovarian cancer and pleural mesothelioma. This review focuses on human CD157 expression and functions and provides an overview on its role in human pathology and its emerging potential as target for antibody-mediated immunotherapy.

Diagnosis of paroxysmal nocturnal hemoglobinuria with flowcytometry panels including CD157: Data from the real world

“…The series of ICCS Guidelines for PNH testing by flow cytometry based on reagent cocktails, including those with FLAER, have greatly increased the standardization of the diagnosis of PNH worldwide. CD157, which is abundantly expressed by blood cells in the myeloid lineage (from precursors to differentiated stages), is expressed by bone marrow stromal cells, synovial cells, endothelial cells, and other cell types and is a key player in regulating leukocyte adhesion, migration, and diapedesis (Ortolan, Augeri, Fissolo, Musso, & Funaro, ). CD157 was recently evaluated to determine its usefulness in PNH diagnosis as a substitute for CD24 and CD14 and to evaluate whether it is a suitable substitute for FLAER that maintains an acceptable diagnostic sensitivity and specificity when combined with other GPI‐anchored proteins (Marinov et al, ; Sutherland et al, ).…”

The Roles of CD38 and CD157 in the Solid Tumor Microenvironment and Cancer Immunotherapy

“…Both CD38 and CD157 have ADP-ribosyl cyclase activity and can convert NAD+ into cADPR, although the cyclase activity of CD157 is hundred times less efficient than that of CD38 [10,36]. However, CD157's hydrolase and cyclase activities are significantly increased by an acidic environment, as well as by the presence of zinc and magnesium ions [10,12,36]. cADPR is a potent mediator of calcium release into the cytosol, and the ability of CD157 to synthesize cADPR implies that, like CD38, it is involved in calcium homeostasis.…”

“…In contrast, CD157 is mainly expressed by cells derived from the myeloid lineage, and in particular by neutrophils and monocytes. CD157 is also expressed by a wide range of non-lymphoid tissues, including vascular endothelium, kidney collecting tubules and Paneth cells in the stomach [12].Both CD38 and CD157 have been used as therapeutic targets in clinical trials to treat solid tumors [12][13][14][15]. This review aims to give an overview of their roles of in the TME, which might provide insights for therapeutic strategies across various cancers.…”

“…In contrast, CD157 is mainly expressed by cells derived from the myeloid lineage, and in particular by neutrophils and monocytes. CD157 is also expressed by a wide range of non-lymphoid tissues, including vascular endothelium, kidney collecting tubules and Paneth cells in the stomach [12].…”

“…Both CD38 and CD157 have been used as therapeutic targets in clinical trials to treat solid tumors [12][13][14][15]. This review aims to give an overview of their roles of in the TME, which might provide insights for therapeutic strategies across various cancers.…”