ArticleCell reports. Medicine2025
Inhibiting KRAS with CD47 and immune checkpoint overcomes intrinsic resistance to combined KRAS and immune checkpoint inhibitor therapy.
Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- KRAS G12C inhibitors in KRASFrontiers in immunology · 2026Pooled it
- Tumor immune microenvironment facilitates resistance to KRAS G12C inhibitor sotorasib by altered PD-L1 expression.Journal for immunotherapy of cancer · 2026Article
- Molecular innate immune programs of tumor-associated macrophages in immune checkpoint blockade resistance: a staged framework from suppressive circuitry to translational bottlenecks.Frontiers in immunology · 2026Review
- Targeted therapy for KRAS G12C-mutated colorectal cancer: advances, challenges, and future directions.American journal of cancer research · 2025Review
Corrections and comments
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Authors and funding
27 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although Kirsten rat sarcoma virus (KRAS) G12C inhibitors alter the treatment strategy for patients with KRAS G12C-mutant lung cancer, their efficacy remains insufficient to eliminate tumors. Here, we identify that inhibition of mutant KRAS promotes escape from macrophage phagocytosis by upregulating the expression of cluster of differentiation 47 (CD47) and CD24. These proteins are induced by the binding of FOXA1 to the super-enhancer of CD47 and grainyhead-like transcription factor 2 (GRHL2) to the promoter of CD24, respectively. Whereas the addition of an anti-CD47 antibody restores macrophage phagocytosis, phagocytic macrophages induce programmed death-ligand 1 (PD-L1) expression, resulting in the suppression of CD8 T cell activation. Combination of a KRAS inhibitor with anti-CD47 and anti-PD-L1 antibodies achieves long-term survival in an orthotopic murine model recalcitrant to KRAS inhibition with immune checkpoint therapy. These results suggest that targeting KRAS with an anti-CD47 antibody and immune checkpoint blockade is a promising strategy, especially in immune-cold lung 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.