CD47
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MYC regulates the antitumor immune response through CD47 and PD-L1 Open
Oncogene control of antitumor immunity Recent clinical success of cancer immunotherapy has intensified interest in how tumors normally evade the immune response. Whether and how oncogenes contribute to this process are not well understood.…
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Pre-Clinical Development of a Humanized Anti-CD47 Antibody with Anti-Cancer Therapeutic Potential Open
CD47 is a widely expressed cell surface protein that functions as a regulator of phagocytosis mediated by cells of the innate immune system, such as macrophages and dendritic cells. CD47 serves as the ligand for a receptor on these innate …
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HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells Open
Increased expression of CD47 has been reported to enable cancer cells to evade phagocytosis by macrophages and to promote the cancer stem cell phenotype, but the molecular mechanisms regulating CD47 expression have not been determined. Her…
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CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer Open
Small-cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with limited treatment options. CD47 is a cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha (SIRPα), which serves as a…
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Durable antitumor responses to CD47 blockade require adaptive immune stimulation Open
Significance Therapeutic antitumor antibodies are widely used clinically. CD47 is an antiphagocytic ligand expressed by tumors that binds the inhibitory receptor signal regulatory protein alpha (SIRPα) on phagocytic cells. Interruption of …
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Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling Open
Most studies focus on how intestinal microbiota influence cancer immunotherapy through activating gut immunity. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor …
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Advances in Anti-Tumor Treatments Targeting the CD47/SIRPα Axis Open
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 phago…
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Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo Open
Tumor-associated macrophages (TAMs) represent an important cellular subset within the glioblastoma (WHO grade IV) microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between an…
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Macrophages are critical effectors of antibody therapies for cancer Open
Macrophages are innate immune cells that derive from circulating monocytes, reside in all tissues, and participate in many states of pathology. Macrophages play a dichotomous role in cancer, where they promote tumor growth but also serve a…
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Activating Macrophage‐Mediated Cancer Immunotherapy by Genetically Edited Nanoparticles Open
Immunomodulation of macrophages against cancer has emerged as an encouraging therapeutic strategy. However, there exist two major challenges in effectively activating macrophages for antitumor immunotherapy. First, ligation of signal regul…
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Macrophages eat cancer cells using their own calreticulin as a guide: Roles of TLR and Btk Open
Significance Macrophage-mediated programmed cell removal (PrCR) plays an essential role in tumor surveillance and elimination. Blockade of the don't-eat-me signal CD47 on tumor cells allows already expressed eat-me signals to induce PrCR t…
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Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies Open
In recent years, immunotherapies have been clinically investigated in AML and other myeloid malignancies. While most of these are focused on stimulating the adaptive immune system (including T cell checkpoint inhibitors), several key appro…
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Microglia are effector cells of CD47-SIRPα antiphagocytic axis disruption against glioblastoma Open
Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with fatal outcome. Tumor-associated macrophages and microglia (TAMs) have been found to be major tumor-promoting immune cells in the tumor microenvironment. Hence,…
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Oxygenated phosphatidylethanolamine navigates phagocytosis of ferroptotic cells by interacting with TLR2 Open
During cancer therapy, phagocytic clearance of dead cells plays a vital role in immune homeostasis. The nonapoptotic form of cell death, ferroptosis, exhibits extraordinary potential in tumor treatment. However, the phagocytosis mechanism …
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Molecular Pathways: Activating T Cells after Cancer Cell Phagocytosis from Blockade of CD47 “Don't Eat Me” Signals Open
Recent advances with immunotherapy agents for the treatment of cancer have provided remarkable, and in some cases, curative results. Our laboratory has identified CD47 as an important “don't eat me” signal expressed on malignant cells. Blo…
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Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion Open
Glioblastoma multiforme (GBM) remains the top challenge to radiotherapy with only 25% one-year survival after diagnosis. Here, we reveal that co-enhancement of mitochondrial fatty acid oxidation (FAO) enzymes (CPT1A, CPT2 and ACAD9) and im…
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Designer exosomes for targeted and efficient ferroptosis induction in cancer via chemo-photodynamic therapy Open
Background: Efficient and specific induction of cell death in liver cancer is urgently needed. In this study, we aimed to design an exosome-based platform to deliver ferroptosis inducer (Erastin, Er) and photosensitizer (Rose Bengal, RB) i…
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Emerging phagocytosis checkpoints in cancer immunotherapy Open
Cancer immunotherapy, mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells, has revolutionized the oncology landscape as it utilizes patients’ own immune systems in combating the cancer …
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Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer Open
Background Human pancreatic ductal adenocarcinoma (PDAC) responds poorly to immune checkpoint inhibitor (ICPi). While the mechanism is not completely clear, it has been recognized that tumor microenvironment (TME) plays key roles. We inves…
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STING agonist-loaded, CD47/PD-L1-targeting nanoparticles potentiate antitumor immunity and radiotherapy for glioblastoma Open
As a key component of the standard of care for glioblastoma, radiotherapy induces several immune resistance mechanisms, such as upregulation of CD47 and PD-L1. Here, leveraging these radiotherapy-elicited processes, we generate a bridging-…
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The SIRPα–CD47 immune checkpoint in NK cells Open
Here we report on the existence and functionality of the immune checkpoint signal regulatory protein α (SIRPα) in NK cells and describe how it can be modulated for cell therapy. NK cell SIRPα is up-regulated upon IL-2 stimulation, interact…
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CD47 signaling pathways controlling cellular differentiation and responses to stress Open
CD47 is a widely expressed integral membrane protein that serves as the counter-receptor for the inhibitory phagocyte receptor signal-regulatory protein-α (SIRPα) and as a signaling receptor for the secreted matricellular protein thrombosp…
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A rapid, automated surface protein profiling of single circulating exosomes in human blood Open
Circulating exosomes provide a promising approach to assess novel and dynamic biomarkers in human disease, due to their stability, accessibility and representation of molecules from source cells. However, this potential has been stymied by…
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CD47/SIRPα pathway mediates cancer immune escape and immunotherapy Open
The adaptive immune checkpoints such as PD-1(programmed death-1)/PD-L1 (programmed death-ligand 1) play an important role in cancer immunotherapy, whereas increasing evidence suggests that cancer cell evades immune surveillance by innate i…
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ALX148 blocks CD47 and enhances innate and adaptive antitumor immunity with a favorable safety profile Open
CD47 is a widely expressed cell surface protein that functions as an immune checkpoint in cancer. When expressed by tumor cells, CD47 can bind SIRPα on myeloid cells, leading to suppression of tumor cell phagocytosis and other innate immun…
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Role of CD47 in Hematological Malignancies Open
CD47, or integrin-associated protein, is a cell surface ligand expressed in low levels by nearly all cells of the body. It plays an integral role in various immune responses as well as autoimmunity, by sending a potent “don’t eat me” signa…
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Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy Open
Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein …
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Thrombospondin-1 is a multifaceted player in tumor progression Open
Thrombospondins are a family of extracellular matrix (ECM) proteins. Thrombospondin-1 (TSP1) was the first member to be identified and is a main player in tumor microenvironment. The diverse functions of TSP1 depend on the interactions bet…
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A bispecific antibody targeting CD47 and CD20 selectively binds and eliminates dual antigen expressing lymphoma cells Open
Agents that block the anti-phagocytic signal CD47 can synergize with pro-phagocytic anti-tumor antigen antibodies to potently eliminate tumors. While CD47 is overexpressed on cancer cells, its expression in many normal tissues may create a…
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Cd47-Sirpα interaction and IL-10 constrain inflammation-induced macrophage phagocytosis of healthy self-cells Open
Significance The present study reveals that macrophage phagocytosis toward healthy self-cells is controlled by a two-tier mechanism: a forefront activation mechanism requiring the inflammatory cytokine-stimulated protein kinase C (PKC)-spl…