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.

It acts as myeloid immune checkpoint and thus has prognostic and therapeutic implications. Areas covered : This review presents and discusses the currently available data on the prognostic role and therapeutic value of CD47 in gastrointestinal tumors. The CD47 gene is located on chromosome 3q13 and encodes an integrin-associated protein. CD47 is an important “self-labeling” molecule in the immunoglobulin superfamily that contains an immunoglobulin variable-like amino-terminal domain, five transmembrane domains, and one carboxy-terminal intracellular tail (34, 35). CD47 is found to be overexpressed on tumor cells and act as a don’t eat me’ signal, which contributes to immune evasion. Macrophages mediated phagocytosis via blockade CD47/SIRPα (signal regulatory protein alpha) interaction was proved to induce effective antitumor immune response.

Among the various approaches to immunotherapy, the targeting of CD47 has been a subject of intense interest. The CD47‐signal regulatory protein α (SIRPα) signaling system and its role in the regulation of phagocytosis by macrophages. A, SIRPα is a transmembrane protein that contains 3 Ig‐like domains (1 V‐like and 2 C1‐like Ig domains) in its NH 2 ‐terminal extracellular region and 2 key tyrosine phosphorylation sites in its COOH‐terminal cytoplasmic region. NIH investigators hope CD47 study leads to broad-spectrum infectious diseases immunotherapy Colorized scanning electron micrograph of a cell (purple) infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. anti-CD47 immunotherapy (Chao et al., 2011; Horrigan and Reproducibility Project: Cancer Biology, 2017; Willingham et al., 2012). Together, those findings raise the possibility that gut microbiota influence anti-CD47 immunotherapy through changing the local microenvironment, challenging the current gut immunity-initiated model.

Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.

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.

Dec 11, 2019 Targeting CD47 could trigger macrophage-mediated elimination of between anti-angiogenic therapy and tumor immunotherapy [17,18,19]. Mar 6, 2020 The gut microbiome modulates gut immunity and affects the host response to cancer immunotherapy, but how microbiota influence the tumor Moreover, MM cells had remarkably higher CD47 expression than other cell that macrophage checkpoint immunotherapy by blocking the CD47 “don't eat me” Jul 26, 2019 The CD47/SIRPα axis is therefore a known major pathway for immune evasion by tumor cells, and is being investigated as an immunotherapy Oct 31, 2018 Anti-CD47 cancer therapy safe, shows promise in small clinical trial. An immunotherapy conceived at Stanford appeared safe in an early Sep 9, 2020 the latest in a string of large biopharma companies making moves into the emerging space of cancer immunotherapy drugs targeting CD47.

Further, blocking of CD47 using an anti-CD47 antibody induced immediate activation of macrophages, which resulted in induction of phagocytosis and killing of MM cells in the 3D-tissue engineered bone marrow model, as early as 4 hours. These results suggest that macrophage checkpoint immunotherapy by blocking the CD47 “don’t eat me”

Their new study in mBio describes this brake and the way pathogens such as SARS-CoV-2, the virus that causes COVID-19, turn it on.

Murata Y(1), Saito Y(1), Kotani T(1), Matozaki T(1). Author information: (1)Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan. 2017-02-14 · Here, a surgical debulking GBM xenograft model was developed in nude rats, and was used in combination with CD47 blocking immunotherapy, a novel treatment strategy that triggers phagocytosis of tumor cells by macrophages in diverse cancer types including GBM. 2021-03-17 · Anti-CD47/PD-L1 immunotherapies aiming to enhance antitumor immunity are being intensively investigated and show promising results in cancer therapy; however, not all patients treated with these Se hela listan på frontiersin.org The researchers suggest that gut bacteria can penetrate tumor cells and boost the effectiveness of experimental immunotherapy that targets the CD47 protein. Methods CD47 is a critical self-protective “don’t eat me” signal on multiple human cancers against macrophage immunosurveillance. Using human and mouse TNBC preclinical models, we evaluated the efficacy of PrCR-based immunotherapy by blocking CD47. 2020-04-02 · CD47 is an immune checkpoint protein that downregulates both the innate and adaptive anti-tumor immune response via its counter receptor SIRPα. Biologics, including humanized CD47 monoclonal antibodies and decoy SIRPα receptors, that block the SIRPα-CD47 interaction, are currently being developed as cancer immunotherapy agents.
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Indeed, CD47 blockade with A4 did not synergize with αCTLA-4 in the 2020-03-06 CD47, an innate immune checkpoint inhibitor is suggested to be the most prominent ‘do not eat me’ signal expressed on the cancer cells surface. CD47 is expressed ubiquitously but significantly upregulated in several human malignancies including breast cancer, colon cancer, prostate cancer, ovarian cancer and hepatocellular carcinoma [ 1, 2 ].

Thus, developing new immunotherapy agents or combination treatments to enhance the efficacy of immunotherapy is an urgent challenge. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor microenvironment.
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NIH investigators hope CD47 study leads to broad-spectrum infectious diseases immunotherapy Colorized scanning electron micrograph of a cell (purple) infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.

CD47 blockade as an adjuvant immunotherapy for resectable pancreatic cancer. Clin. Cancer Res. 24, 1415–1425 (2018). anti-CD47 immunotherapy (Chao et al., 2011; Horrigan and Reproducibility Project: Cancer Biology, 2017; Willingham et al., 2012). Together, those findings raise the possibility that gut microbiota influence anti-CD47 immunotherapy through changing the local microenvironment, challenging the current gut immunity-initiated model. Our study iden- However, the antitumor efficacy of CD47-based immunotherapy relies on the near-complete blockade of CD47 in the tumor microenvironment (TME; Ingram et al., 2017). To specify the location of antitumor effects of gut microbiota that interacted with CD47 blockade, we used very low doses of antibiotic therapy inside tumor tissues.

Feb 14, 2017 The success of combination treatment including surgery and CD47 blocking immunotherapy is dependent on expression of CD47 in tumor cells.

anti-CD47 immunotherapy (Chao et al., 2011; Horrigan and Reproducibility Project: Cancer Biology, 2017; Willingham et al., 2012). Together, those findings raise the possibility that gut microbiota influence anti-CD47 immunotherapy through changing the local microenvironment, challenging the current gut immunity-initiated model. Our study iden- However, the antitumor efficacy of CD47-based immunotherapy relies on the near-complete blockade of CD47 in the tumor microenvironment (TME; Ingram et al., 2017). To specify the location of antitumor effects of gut microbiota that interacted with CD47 blockade, we used very low doses of antibiotic therapy inside tumor tissues.

CD47, a multi-facetted target for cancer immunotherapy. Atlas of Genetics and Cytogenetics in Oncology and Haematology website. http ancer immune responses. Here, we treated carcinogen-induced or transplantable mouse models of cancer by a CD47 blocking antibody that was at least as efficient as chemotherapy and that could be favorably combined with the anthracycline mitoxantrone in the context of carcinogen-induced ortho- 2021-03-01 2021-03-17 2019-03-14 2018-08-28 Multiple myeloma (MM) remains to be incurable despite recent therapeutic advances. CD47, an immune checkpoint known as the “don’t eat me” signal, is highly expressed on the surface of various cancers, allowing cancer cells to send inhibitory signals to macrophages and impede phagocytosis and immune response. In this study, we hypothesized that blocking the “don’t eat me&rdquo 2018-12-11 The CD47-SIRPα signaling axis functions as an innate immune checkpoint that inhibits phagocytosis in phagocytes and has been implicated as a promising target for cancer immunotherapy. The potential of macrocyclic peptides that target this signaling axis as immunotherapeutic agents has remained unknown, however.