Abstract
CD47 is a cell surface protein in the immunoglobulin superfamily which is normally expressed at low levels in every healthy cell. It´s main physiologic function is to act as an inhibitor of phagocytosis; this occurs throughout interaction with SIRPa expressed on macrophages. Interaction between CD47 and SIRPa leads to activation of tyrosine phosphatases that inhibit myosin accumulation at the submembrane assembly site of the phagocytic synapse, resulting in phagocytosis blockade. In this way CD47 acts as a “don´t eat me signal” for healthy self-cells; accordingly, loss of CD47 leads to phagocytosis of aged or damaged cells. Taking advantage of this anti-phagocytic signal provided by CD47, many types of tumors overexpress this protein, thereby avoiding phagocytosis by macrophages and aiding in the survival of cancer cells. The aim of this review is to describe the physiologic the pathophysiologic role of CD47; summarize the available high-quality information about this molecule as a potential biomarker and/or therapeutic target in cancer; finally, we present an in-depth analysis of the available information about CD47 in association with nonsmall cell lung cancer, EGFR mutations, and tumor microenvironment.
Highlights
The role of CD47 on immune recognition and phagocytosis was first described by Oldenborg et al, in 2000; their research demonstrated that healthy red blood cells (RBC) that are derived from CD47-/- mice were rapidly cleared when Journal of Immunology Research
Their results indicate that CD47 is one of the major components of red blood cells (RBCs) aging “clock,” which act by inhibiting erythrocyte phagocytosis until CD47 levels at RBCs membrane fall below the phagocytosis-inhibitory concentration, and RBCs are phagocyted by macrophages at the spleen [5]
In line with the evidence provided by treating nonHodgkin’s lymphoma (NHL) with Magrolimab plus rituximab, we consider that anti-CD47 drugs should be promptly tested in combination with other directed therapies, such as antiangiogenic therapy and tyrosine-kinase inhibitors, that have proved to be efficient for the treatment of nonsmall cell lung cancer (NSCLC) (Figure 2)
Summary
CD47 is a transmembrane protein ubiquitously expressed in almost every healthy cell; it was first purified by Lindberg et al, in 1993 [1]. Transfused to wild-type recipient mice; they proved that this effect was reversed when macrophages were depleted using clodronate liposome [5] Their results indicate that CD47 is one of the major components of red blood cells (RBCs) aging “clock,” which act by inhibiting erythrocyte phagocytosis until CD47 levels at RBCs membrane fall below the phagocytosis-inhibitory concentration, and RBCs are phagocyted by macrophages at the spleen [5]. Another pivotal experiment, which was published by Ishikawa-Sekigami et al, consisted in transferring normal RBC to mice lacking the ITIM domain of SIRPα; their results demonstrated that erythrocytes were rapidly phagocytosed, even when CD47 expression was high. This merely reflects a general lack of experimental data; it should be noted that the effects of TSP-1 on CD-47 are beyond the scope of the present review
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