Subtopic Deep Dive

Role of CD47 in Phagocytosis Regulation
Research Guide

What is Role of CD47 in Phagocytosis Regulation?

CD47 acts as a 'don't eat me' signal by binding SIRPα on phagocytes to inhibit phagocytosis of healthy and tumor cells.

CD47-SIRPα interaction delivers inhibitory signals preventing macrophage engulfment (Willingham et al., 2012, 1604 citations). Overexpression on solid tumors enables immune evasion, targeted by blocking antibodies (Feng et al., 2019, 888 citations). Structural studies detail the binding interface for therapeutic design (Barclay and van den Berg, 2013, 803 citations).

Curated Papers

Key Challenges

Why It Matters

CD47 blockade enhances tumor phagocytosis, powering macrophage-based immunotherapies for solid tumors like small-cell lung cancer (Willingham et al., 2012; Weiskopf et al., 2016). In autoimmune settings, CD47-SIRPα regulates RBC clearance by splenic macrophages (Oldenborg et al., 2001). Developmental roles protect synapses from microglial pruning (Lehrman et al., 2018). Nanovesicle engineering amplifies macrophage responses post-CD47 targeting (Rao et al., 2020).

Key Research Challenges

Anemia from CD47 Blockade

Therapeutic CD47 antibodies cause transient anemia by promoting healthy RBC phagocytosis (Oldenborg et al., 2001). Balancing tumor clearance against self-cell protection remains critical (Feng et al., 2019). Engineering selective inhibitors addresses this toxicity.

Synaptic Pruning Disruption

CD47 knockout increases microglia-mediated synapse loss during development (Lehrman et al., 2018). Systemic blockade risks neurodevelopmental side effects. Targeted delivery limits off-target neuronal impacts.

Resistance in Solid Tumors

Heterogeneous CD47 expression limits uniform phagocytosis induction (Willingham et al., 2012). Adaptive tumor evasion post-blockade requires combination therapies (Veillette and Chen, 2018). Biomarker stratification improves patient selection.

Essential Papers

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

Stephen B. Willingham, Jens-Peter Volkmer, Andrew J. Gentles et al. · 2012 · Proceedings of the National Academy of Sciences · 1.6K citations

CD47, a “don't eat me” signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that...

Phagocytosis checkpoints as new targets for cancer immunotherapy

Mingye Feng, Wen Jiang, Betty Y.S. Kim et al. · 2019 · Nature reviews. Cancer · 888 citations

The Interaction Between Signal Regulatory Protein Alpha (SIRPα) and CD47: Structure, Function, and Therapeutic Target

A. Neil Barclay, Timo K. van den Berg · 2013 · Annual Review of Immunology · 803 citations

CD47 is a broadly expressed membrane protein that interacts with the myeloid inhibitory immunoreceptor SIRPα (also termed CD172a or SHPS-1). SIRPα is the prototypic member of the SIRP paired recept...

Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells

Richard Tsai, Dennis E. Discher · 2008 · The Journal of Cell Biology · 466 citations

Phagocytosis of foreign cells or particles by macrophages is a rapid process that is inefficient when faced with “self” cells that display CD47—although signaling mechanisms in self-recognition hav...

Cd47-Signal Regulatory Protein α (Sirpα) Regulates Fcγ and Complement Receptor–Mediated Phagocytosis

Per‐Arne Oldenborg, Hattie D. Gresham, Frederik P. Lindberg · 2001 · The Journal of Experimental Medicine · 451 citations

In autoimmune hemolytic anemia (AIHA), circulating red blood cells (RBCs) opsonized with autoantibody are recognized by macrophage Fcγ and complement receptors. This triggers phagocytosis and elimi...

SIRPα–CD47 Immune Checkpoint Blockade in Anticancer Therapy

André Veillette, Jun Chen · 2018 · Trends in Immunology · 448 citations

CD47 Protects Synapses from Excess Microglia-Mediated Pruning during Development

Emily K. Lehrman, Daniel K. Wilton, Elizabeth Y. Litvina et al. · 2018 · Neuron · 446 citations

Reading Guide

Foundational Papers

Start with Oldenborg et al. (2001) for RBC phagocytosis regulation (451 citations), then Willingham et al. (2012) for tumor targeting (1604 citations), and Barclay and van den Berg (2013) for structural mechanisms (803 citations).

Recent Advances

Study Feng et al. (2019) for immunotherapy checkpoints (888 citations), Weiskopf et al. (2016) for SCLC applications (421 citations), and Rao et al. (2020) for nanovesicle enhancements (358 citations).

Core Methods

Phagocytic index assays quantify engulfment; flow cytometry measures CD47 expression; blocking antibodies test SIRPα inhibition; molecular dynamics simulate binding (Tsai and Discher, 2008; Barclay and van den Berg, 2013).

How PapersFlow Helps You Research Role of CD47 in Phagocytosis Regulation

Discover & Search

Research Agent uses searchPapers and citationGraph to map CD47-SIRPα literature from Willingham et al. (2012, 1604 citations) to Feng et al. (2019), revealing 888-citation reviews. exaSearch uncovers nanovesicle applications like Rao et al. (2020); findSimilarPapers extends to SCLC therapies (Weiskopf et al., 2016).

Analyze & Verify

Analysis Agent applies readPaperContent to extract myosin-II deactivation mechanisms from Tsai and Discher (2008), then verifyResponse with CoVe checks claims against Oldenborg et al. (2001). runPythonAnalysis processes phagocytosis rates from RBC datasets with pandas, graded by GRADE for evidence strength in anemia risks.

Synthesize & Write

Synthesis Agent detects gaps in synapse protection post-blockade (Lehrman et al., 2018), flagging contradictions with tumor data. Writing Agent uses latexEditText for methods sections, latexSyncCitations for 10+ papers, latexCompile for figures, and exportMermaid for CD47-SIRPα signaling diagrams.

Use Cases

"Quantify CD47 expression differences in tumor vs normal tissues from patient data."

Research Agent → searchPapers('CD47 tumor expression') → Analysis Agent → runPythonAnalysis(pandas on Willingham et al. 2012 datasets) → matplotlib plots of log2 fold-changes with statistical p-values.

"Write LaTeX review on CD47 blockade anemia risks."

Synthesis Agent → gap detection across Oldenborg 2001 + Feng 2019 → Writing Agent → latexEditText(draft) → latexSyncCitations(5 papers) → latexCompile(PDF) with phagocytic synapse figure.

"Find code for CD47-SIRPα binding simulations."

Research Agent → paperExtractUrls(Barclay 2013) → Code Discovery → paperFindGithubRepo → githubRepoInspect → verified molecular dynamics scripts for affinity calculations.

Automated Workflows

Deep Research workflow conducts systematic review of 50+ CD47 papers: searchPapers → citationGraph → DeepScan (7-step verification with CoVe on anemia claims from Oldenborg 2001). Theorizer generates hypotheses on nanovesicle synergies (Rao 2020 + Weiskopf 2016), outputting Mermaid signaling models. DeepScan analyzes SCLC resistance with GRADE grading of Weiskopf et al. (2016).

Try Doxa for Role of CD47 in Phagocytosis Regulation Research

Frequently Asked Questions

What defines CD47's role in phagocytosis?

CD47 binds SIRPα on macrophages to transduce 'don't eat me' signals via myosin-II deactivation (Tsai and Discher, 2008; Barclay and van den Berg, 2013).

What methods study CD47-SIRPα inhibition?

Phagocytosis assays measure engulfment of CD47-expressing cells by macrophages; blocking antibodies test therapeutic potential (Willingham et al., 2012; Weiskopf et al., 2016).

What are key papers on CD47 in cancer?

Willingham et al. (2012, 1604 citations) showed CD47 overexpression on solid tumors; Feng et al. (2019, 888 citations) reviewed phagocytosis checkpoints; Weiskopf et al. (2016, 421 citations) demonstrated SCLC clearance.

What open problems exist in CD47 research?

Reducing anemia toxicity from blockade (Oldenborg et al., 2001); preventing synaptic over-pruning (Lehrman et al., 2018); overcoming tumor resistance via combinations (Veillette and Chen, 2018).