Role of CD47 in Hematological Malignancies

Abstract

CD47, or integrin-associated protein, is a cell surface ligand expressed in low levels by nearly all cells of the body. It plays an integral role in various immune responses as well as autoimmunity, by sending a potent "don't eat me" signal to prevent phagocytosis. A growing body of evidence demonstrates that CD47 is overexpressed in various hematological malignancies and its interaction with SIRPα on the phagocytic cells prevents phagocytosis of cancer cells. Additionally, it is expressed by different cell types in the tumor microenvironment and is required for establishing tumor metastasis. Overexpression of CD47 is thus often associated with poor clinical outcomes. CD47 has emerged as a potential therapeutic target and is being investigated in various preclinical studies as well as clinical trials to prove its safety and efficacy in treating hematological neoplasms. This review focuses on different therapeutic mechanisms to target CD47, either alone or in combination with other cell surface markers, and its pivotal role in impairing tumor growth and metastatic spread of various types of hematological malignancies.

CD47 expression and CD163+ macrophages correlated with prognosis of pancreatic neuroendocrine tumor

“…It is worth to mention that CD47 may mediate many different biologic activities besides its immunoregulatory functions. CD47 is not only a receptor for SIRP and the matricellular protein thrombospondin-1 (TSP-1), but also for ligands that are emerging [ 40 ]. Evidence has indicated that CD47 is a versatile factor in cell activity, such as in angiogenesis [ 41 , 42 ], cell migration, immune-cell filtration [ 43 ], as well as cell death [ 44 ].…”

Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia

“…However, the correlation between U-CLL and CD38 expression was not found in another study [48]. Higher levels of CD47 are also related to U-CLL [49]. Compared to M-CLL, U-CLL is 4 times more likely to develop Richter syndrome (RS) [38].…”

Acute Myeloid Leukemia Stem Cells: The Challenges of Phenotypic Heterogeneity

“…Lately, enhanced CD47 expression was linked to CD123 expression and shown to be responsible for drug resistance in AML that could be overcome by treatment with the histone deacetylase inhibitor Romidepsin [ 126 ]. However, phase 1 trials using monoclonal anti-CD47 antibodies were terminated due to insufficient activity (CC-90002, NCT02641002) [ 127 ], life threatening side effects (Ti-061, 2016-004372-22; Hu5F9-g4, NCT02678338), or anemia (due to CD47 expression on red blood cells [ 128 ]). Results from other currently recruiting clinical trials are underway.…”