Is CD47 an innate immune checkpoint for tumor evasion?

Abstract

Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. One essential mechanism behind CD47-mediated immune evasion is that it can interact with signal regulatory protein-alpha (SIRPα) expressed on myeloid cells, causing phosphorylation of the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and recruitment of Src homology 2 domain-containing tyrosine phosphatases to ultimately result in delivering an anti-phagocytic—“don’t eat me”—signal. Given its essential role as a negative checkpoint for innate immunity and subsequent adaptive immunity, CD47-SIRPα axis has been explored as a new target for cancer immunotherapy and its disruption has demonstrated great therapeutic promise. Indeed, CD47 blocking antibodies have been found to decrease primary tumor size and/or metastasis in various pre-clinical models. In this review, we highlight the various functions of CD47, discuss anti-tumor responses generated by both the innate and adaptive immune systems as a consequence of administering anti-CD47 blocking antibody, and finally elaborate on the clinical potential of CD47 blockade. We argue that CD47 is a checkpoint molecule for both innate and adaptive immunity for tumor evasion and is thus a promising target for cancer immunotherapy.

Characterization of cluster of differentiation�47 expression and its potential as a therapeutic target in esophageal squamous cell cancer

“…CD47 is recognized as a checkpoint for the innate immune response and delivers an inhibitory signal when it binds with SIRPα expressed on phagocytes (30)(31)(32). Anti-CD47 treat-30-32).…”

Targeting CD47: the achievements and concerns of current studies on cancer immunotherapy

“…At least three CD47 antagonists (Hu5F9-G4, CC-90002, and TTI-621) ( Table 1) are currently in active phase I clinical trials, covering hematological malignancies and solid tumors (4). With the release of their safety profiles (5-7), more attention is now being focused on comparing the side effects (8) and efficacies of these inhibitory reagents.…”

Human expression patterns: qualitative and quantitative analysis of thrombospondin‐1 under physiological and pathological conditions

“…Accumulating evidence has suggested that the TSP‐1/CD47 axis could be a promising therapeutic target in cancer as well as in cardiovascular diseases . Besides its well‐established anti‐angiogenic and anti‐proliferative effects when engaged with TSP‐1, CD47 also participates in immune suppression of macrophages and is found widely overexpressed in different types of cancer . As a self‐recognition signal, CD47 on cancer cells associates with SIRPα (signal regulatory protein alpha) on macrophages and inhibits phagocytic activities.…”

“…CD47 also participates in immune suppression of macrophages and is found widely overexpressed in different types of cancer. 122 As a selfrecognition signal, CD47 on cancer cells associates with SIRPa (signal regulatory protein alpha) on macrophages and inhibits phagocytic activities. Interestingly, TSP-1 also interacts with SIRPa expressed on non-phagocytic cells; however, the potential role of how TSP-1 modulates the CD47/SIRPa axis during macrophage activation remains unclear.…”