Polymorphisms in the human inhibitory signal-regulatory protein alpha do not affect binding to its ligand CD47. SIRPA plays a protective role in cardiac hypertrophy through negative regulation of the Toll-like receptor 4/nuclear factor-kappaB pathway.
The CD47/signal regulatory protein alpha (SIRPα) axis is a critical regulator of myeloid cell activation and serves a broader role as a myeloid-specific immune checkpoint. CD47 is highly expressed on many different types of cancer, and it transduces inhibitory signals through SIRPα on macrophages and other myeloid cells. The CD47-SIRPα mechanism was first reported by Oldenborg et al. , who had demonstrated in red blood cell (RBC) transfusion experiments that WT mice rapidly eliminate syngeneic Cd47-null (Cd47 −) RBCs through erythrophagocytosis in the spleen and that the lack of tyrosine phosphorylation in SIRPα ITIMs was associated with this macrophage aggressiveness. Blocking the CD47-SIRPa axis by delivery of anti-CD47 antibody induces antitumor effects in glioma and glioma stem cells Feng Li #, Bingke Lv , Yang Liu, Tian Hua, Jianbang Han, Chengmei Sun, Limin Xu, Zhongfei Zhang, Zhiming Feng, Yingqian Cai, Yuxi Zou, Yiquan Ke, and Xiaodan Jiang Purpose: CD47 plays a variety of roles in intercellular signaling. Herein, we focused on the clinicopathologic significance of CD47 expression in human breast cancer.
Together, the results demonstrate that disruption of the SIRPα–CD47 immune checkpoint may augment NK cell antitumor responses and that elevated expression of CD47 may prevent NK cell–mediated killing of allogeneic and xenogeneic tissues. SIRPa–CD47 blockade, and highlight key issues for future investigations. These include the targeting of prophagocytic receptors (Fc receptors or other-wise) to complement SIRPa–CD47 blockade, the understanding of constraints on phagocytosis other than the SIRPa–CD47 checkpoint and the contribution of immune cells other than macrophages. 2016-09-13 CD47/SIRPa Summit Agenda - CD47/SIRPα Summit. Panel Discussion: What Impact is our Current Level of Understanding of the CD47|SIRPα Checkpoint Having on the Industry? This protein is CD47 (Integrin-Associated Protein/IAP), which is recognized by the inhibitory receptor SIRPa (SHPS-1/BIT/P84) on Mf or DC. The interaction of these two proteins does not only regulate phagocytosis in Mf or DC in contact with another host cell, it is also found in neural tissues where it may be involved in regulating migration of nerve cells, formation of cell protrusions, and 2021-03-22 2021-03-01 2015-01-26 High tumor CD47 expression (HR = 1.75), lymph node metastasis (HR = 2.26), and peritoneal metastasis (HR = 5.80) were cited as potential independent risk factors.
Inhibitory immune checkpoint blockade has been one of the most significant advances in anticancer therapy of the past decade. Research so far has largely focused on improving adaptive immune functions, but recent studies have indicated that the signal-regulatory protein (SIRP)α-CD47 pathway, a phago …
Rac1/Akt signaling pathway in VM neurons was activated by CD47-SIRPA interaction between Treg cells and the neurons. CD47 is highly expressed on many different types of cancer, and it transduces inhibitory signals through SIRPα on macrophages and other myeloid cells.
Mark P. Chao,et al. Curr Opin Immunol. 2012, 24(2): 225–232. 目前SIRPα和CD47靶点的药物研发进展：尚未有上市药物，继天境生物CD47抗体TJC4 在1月25日获批FDA临床试验许可后，9个药物已进入临床初期阶段（国内已有4家成功抢占先机），临床前研究药物9个以上。
NYHET Proteinerna CD47 och SIRPα är viktiga för att utvecklingen av (Engelsk titel: Defining the role of CD47 and SIRPa in murine B cell Proteinerna CD47 och SIRPα är viktiga för att utvecklingen av antalet vita (Engelsk titel: Defining the role of CD47 and SIRPa in murine B cell får 1 650 000 kr för projektet ”Betydelsen av CD47/SIRPa-interaktion för osteoklastbildning från hematopoetiska celler”. Tel. 090-786 59 74. TTI-621 acts by binding human CD47 and preventing it from delivering an inhibitory "do not eat" (antiphagocytic) signal to macrophages. The study will be Kan vara en närbild av 1 person, hår och ytterplagg. Kan vara en bild av text där det står ”(a) SIRPa Efferocytosis CD47 · Institute for Quantitative Health Science får 1 650 000 kr för projektet ”Betydelsen av CD47/SIRPa-interaktion för osteoklastbildning från hematopoetiska celler”. Tel. 090-786 59 74. cancer immune evasion now includes CTLA-4, PD-1/PD-L1, CD27/CD70, FGL-1/LAG-3, Siglec-15, VISTA (PD-1L)/VSIG3, CD47/SIRPA, APOE/LILRB4, TIGIT, Konferens: Bone Biology Joint Meeting 2008, Stockholm/Åbo, Titel: CD47, SIRPa andosteoclastogenesis2.
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If you are not able to attend any of the conferences in person, this Analytical CD47 is a transmembrane protein expressed the surface of many cells in the body. SIRPa, which is expressed on phagocytic cells, was identified as the receptor of CD47. Engagement of SIRPa by CD47 serves as “do not eat me” signal, thus inhibiting the phagocytic activity of macrophages. Antibodies blocking the CD47-SIRPa interaction will release such […] The CD47|SIRPα Summit Goes Online for 2020.
The CD47/signal regulatory protein alpha (SIRPα) axis is a critical regulator of myeloid cell activation and serves a broader role as a myeloid-specific immune checkpoint.
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The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci U S A . 2012;109(17):6662–6667. View this article via: PubMed CrossRef Google Scholar
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Summary. CD47 acts as a “don’t eat me” signal that protects cells from phagocytosis by binding and activating its receptor SIPRA on macrophages. CD47 suppresses multiple different pro-engulfment “eat me” signals, including immunoglobulin G (IgG), complement, and calreticulin, on distinct target cells.
CD47 is overexpressed in cancer cells and its expression is asso-ciated with poor clinical outcomes. TTI-621 (SIRPaFc) is a fully humanrecombinant fusionproteinthatblocksthe CD47–SIRPa CD47/SIRPα, AN IMMUNE CHECKPOINT FORINNATE IMMUNE SYSTEM. Among cells of the myeloid lineage, macrophage has prominent potentials as the mediator of anti-cancer therapeutics based on its robust phagocytosis ability [8, 9]. CD47, known as an integrin-associated protein, was first identified as a transmembrane protein from red blood cells (RBC) . Has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins. Plays an important role in memory formation and synaptic plasticity in the hippocampus (By similarity).
Mark P. Chao,et al. Curr Opin Immunol. 2012, 24(2): 225–232.