ArticleThe Journal of clinical investigation2023
Oncogenic KRAS signaling drives evasion of innate immune surveillance in lung adenocarcinoma by activating CD47.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
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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
63 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Current status of KRAS G12C inhibitors in NSCLC and the potential for combination with anti-PD-(L)1 therapy: a systematic review.Frontiers in immunology · 2025Pooled it
- Recent advances in the regulation of CD47 by non-coding RNAs and its therapeutic potential in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- KRAS Inhibitor-Induced Cancer Cell Death Enhances Sensitivity to Immune-Mediated Bystander Killing of Drug-Resistant Subclones.Cancer research · 2026Article
- Review
- CD47 promotes mitogen-activated protein kinase and epithelial-to-mesenchymal transition molecular programs to drive prometastatic phenotypes in non-small cell lung cancer.Molecular oncology · 2026Article
- KRAS and MYC synergistic inhibition: a powerful strategy targeting KRAS-mutant cancers.Molecular cancer · 2026Review
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- The identification of RNA splicing aberrations and their potential regulatory network in Chinese non-small cell lung cancer.Respiratory research · 2026Article
- Core Fucosylation Represses SMURF1-Dependent Degradation of CD47 to Promote Tumor Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Loss of MicroRNA-29b promotes DNMT3b-mediated STING downregulation to attenuate radiotherapy-induced antitumor immunity in KRAS-mutated colorectal cancer.NPJ precision oncology · 2026Article
- Avidity-optimized TCR-T cells target KRAS neoantigens for potent cancer clearance and tumor microenvironment remodeling.Frontiers in immunology · 2026Article
- Oncogenic KRAS mutations drive immune suppression through immune-related regulatory network and metabolic reprogramming.Cell death & disease · 2025Review
- Distinct molecular subtypes of KRASClinical and translational medicine · 2025Article
- Engineered exosomes: a promising approach for overcoming challenges in pancreatic cancer therapy.Journal of nanobiotechnology · 2025Review
- Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.Chinese medical journal · 2025Review
- Inhibiting KRAS with CD47 and immune checkpoint overcomes intrinsic resistance to combined KRAS and immune checkpoint inhibitor therapy.Cell reports. Medicine · 2025Article
- KRAS mutation promotes immune escape of lung adenocarcinoma via ZNF24/SLC7A5/PD-L1 axis.BMC cancer · 2025Article
- Targeting MAN1B1 potently enhances bladder cancer antitumor immunity via deglycosylation of CD47.Cancer communications (London, England) · 2025Article
- Targeting KRAS in colorectal cancer (Review).Molecular and clinical oncology · 2025Review
- Mechanistic Foundations of KRAS-Driven Tumor Ecosystems: Integrating Crosstalk among Immune, Metabolic, Microbial, and Stromal Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KRAS is one of the most frequently activated oncogenes in human cancers. Although the role of KRAS mutation in tumorigenesis and tumor maintenance has been extensively studied, the relationship between KRAS and the tumor immune microenvironment is not fully understood. Here, we identified a role of KRAS in driving tumor evasion from innate immune surveillance. In samples of lung adenocarcinoma from patients and Kras-driven genetic mouse models of lung cancer, mutant KRAS activated the expression of cluster of differentiation 47 (CD47), an antiphagocytic signal in cancer cells, leading to decreased phagocytosis of cancer cells by macrophages. Mechanistically, mutant KRAS activated PI3K/STAT3 signaling, which restrained miR-34a expression and relieved the posttranscriptional repression of miR-34a on CD47. In 3 independent cohorts of patients with lung cancer, the KRAS mutation status positively correlated with CD47 expression. Therapeutically, disruption of the KRAS/CD47 signaling axis with KRAS siRNA, the KRASG12C inhibitor AMG 510, or a miR-34a mimic suppressed CD47 expression, enhanced the phagocytic capacity of macrophages, and restored innate immune surveillance. Our results reveal a direct mechanistic link between active KRAS and innate immune evasion and identify CD47 as a major effector underlying the KRAS-mediated immunosuppressive tumor microenvironment.
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