title: 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.
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|Department of Pathology, UT Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Hyunwoo
authors.initials: H
authors.lastname: Kwon
authors.affiliation: Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA. Zihai@musc.edu.|First Affiliated Hospital, Zhengzhou University School of Medicine, Zhengzhou, China. Zihai@musc.edu.
authors.forename: Zihai
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology, UT Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
mesh_terms: D056704:Adaptive Immunity; D000943:Antigens, Differentiation / Q000378:metabolism; D051928:CD47 Antigen / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods; D011971:Receptors, Immunologic / Q000378:metabolism; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D000943:Antigens, Differentiation; D051928:CD47 Antigen; C497894:CD47 protein, human; D011971:Receptors, Immunologic; C501920:SIRPA protein, human
keywords: CD47; Cancer immunotherapy; Chemotherapy; Clinical trial; Dendritic cell; Macrophage; SIRPα; “Don’t eat me” signal