ArticleThe Journal of clinical investigation2020
Selective SIRPα blockade reverses tumor T cell exclusion and overcomes cancer immunotherapy resistance.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical data.Frontiers in immunology · 2022Pooled it
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- Targeting phagocytosis checkpoints for cancer immunotherapy.Nature reviews. Cancer · 2026Review
- The SIRP family: from structural diversity and signaling mechanisms to implications in immune-related disease targeted therapeutics.Frontiers in immunology · 2026Review
- Expression of cluster of differentiation 47 (CD47) and signal regulatory protein alpha (SIRPα) as prognostic biomarkers and potentially therapeutic targets in esophageal squamous cell carcinoma.Esophagus : official journal of the Japan Esophageal Society · 2026Article
- Macrophage-centered therapy strategies: A promising weapon in cancer immunotherapy.Asian journal of pharmaceutical sciences · 2025Review
- Loss of NR2F6 Protects from Salmonella Typhimurium Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Novel immunotherapy for gastric cancer: targeting the CD47-SIRPα axis.Cancer metastasis reviews · 2025Review
- Oncolytic adenovirus H101 enhances the anti-tumor effects of PD-1 blockade via CD47 downregulation in tumor cells.Oncology research · 2025Article
- Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors.Frontiers in immunology · 2025Review
- Deciphering the role of CD47 in cancer immunotherapy.Journal of advanced research · 2024Review
- Disruption of CD47-SIRPα signaling restores inflammatory function in tumor-associated myeloid-derived suppressor cells.iScience · 2024Article
- Sirpα on tumor-associated myeloid cells restrains antitumor immunity in colorectal cancer independent of its interaction with CD47.Nature cancer · 2024Article
- Targeting HDAC6 improves anti-CD47 immunotherapy.Journal of experimental & clinical cancer research : CR · 2024Article
- Discovery and Preclinical Activity of BMS-986351, an Antibody to SIRPα That Enhances Macrophage-mediated Tumor Phagocytosis When Combined with Opsonizing Antibodies.Cancer research communications · 2024Article
- 4-1BB immunotherapy: advances and hurdles.Experimental & molecular medicine · 2024Review
- Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPα axis.Cell communication and signaling : CCS · 2024Article
- Review
- SKAP2-A Molecule at the Crossroads for Integrin Signalling and Immune Cell Migration and Function.Biomedicines · 2023Review
- SIRPα blockade improves the antitumor immunity of radiotherapy in colorectal cancer.Cell death discovery · 2023Article
Corrections and comments
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Authors and funding
43 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell exclusion causes resistance to cancer immunotherapies via immune checkpoint blockade (ICB). Myeloid cells contribute to resistance by expressing signal regulatory protein-α (SIRPα), an inhibitory membrane receptor that interacts with ubiquitous receptor CD47 to control macrophage phagocytosis in the tumor microenvironment. Although CD47/SIRPα-targeting drugs have been assessed in preclinical models, the therapeutic benefit of selectively blocking SIRPα, and not SIRPγ/CD47, in humans remains unknown. We report a potent synergy between selective SIRPα blockade and ICB in increasing memory T cell responses and reverting exclusion in syngeneic and orthotopic tumor models. Selective SIRPα blockade stimulated tumor nest T cell recruitment by restoring murine and human macrophage chemokine secretion and increased anti-tumor T cell responses by promoting tumor-antigen crosspresentation by dendritic cells. However, nonselective SIRPα/SIRPγ blockade targeting CD47 impaired human T cell activation, proliferation, and endothelial transmigration. Selective SIRPα inhibition opens an attractive avenue to overcoming ICB resistance in patients with elevated myeloid cell infiltration in solid tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.