Advances in Anti-Tumor Treatments Targeting the CD47/SIRPα Axis

Abstract

CD47 is an immunoglobulin that is overexpressed on the surface of many types of cancer cells. CD47 forms a signaling complex with signal-regulatory protein α (SIRPα), enabling the escape of these cancer cells from macrophage-mediated phagocytosis. In recent years, CD47 has been shown to be highly expressed by various types of solid tumors and to be associated with poor patient prognosis in various types of cancer. A growing number of studies have since demonstrated that inhibiting the CD47-SIRPα signaling pathway promotes the adaptive immune response and enhances the phagocytosis of tumor cells by macrophages. Improved understanding in this field of research could lead to the development of novel and effective anti-tumor treatments that act through the inhibition of CD47 signaling in cancer cells. In this review, we describe the structure and function of CD47, provide an overview of studies that have aimed to inhibit CD47-dependent avoidance of macrophage-mediated phagocytosis by tumor cells, and assess the potential and challenges for targeting the CD47-SIRPα signaling pathway in anti-cancer therapy.

Establishment of a 3D Co-culture With MDA-MB-231 Breast Cancer Cell Line and Patient-Derived Immune Cells for Application in the Development of Immunotherapies

“…Actually, in cases of metastatic TNBC, immunotherapies against PD-L1 are already approved, namely Atezolizumab along with paclitaxel ( 27 ). Therapies against CD47 are also being applied in several clinical trials, although not specifically in breast cancer ( 25 ).…”

“…This cell line is also positive for the immunosuppressive trait PD-L1, and CD47 ( Figure S1 ), which can be seen as possible targets to develop directed therapies. PD-L1 is an immune checkpoint, which can inhibit the effector function of T cells; while CD47 might help the tumor cells to evade phagocytosis by phagocytic immune cells ( 25 ). The platform here developed, bearing embedded immune cells, could allow to test these and other several immune-modulator agents to develop new TNBC-specific therapies.…”

Plasticity in Pro- and Anti-tumor Activity of Neutrophils: Shifting the Balance

“…Neutrophils express a variety of inhibitory receptors on their cell surface ( 211 ) providing potential therapeutic targets for checkpoint-blockade therapy. One well-established example of successful checkpoint-blockade on neutrophils is CD47-signal regulatory protein alpha (SIRPα) disruption ( 212 ). We and others have already shown the potency of blocking the interaction between CD47 and SIRPα on neutrophils, thereby enhancing the neutrophil’s ADCC capacity against both solid and hematological tumors in vitro and in vivo ( 213 – 215 ).…”

ImmunoPET-informed sequence for focused ultrasound-targeted mCD47 blockade controls glioma

“…Given the burgeoning role of BBB/BTB-D in clinical brain tumor care, these findings also generate compelling insights and important considerations for the delivery of immunotherapeutic antibodies with FUS, all the while expounding a novel paradigm for mCD47 therapy. Clinical development of CD47-targeting therapies is well underway [48], but targeting of CD47 within gliomas has been persistently challenged by presence of the BBB and BTB. Our readily translatable study generates timely evidence for the potential of MR image-guided FUS BBB/BTB-D to surmount this challenge and promote efficacy of mCD47 in the setting of GB.…”