ArticleCell death & disease2024
KEAP1 promotes anti-tumor immunity by inhibiting PD-L1 expression in NSCLC.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 22 citations in OpenAlex.
- Social Network Clustering Analysis for Detection of Associated Genetic Co-Mutations in Patients with Actionable Driver Mutations in NSCLC.Life (Basel, Switzerland) · 2026Article
- Melanoma-patient-derived xenograft multi-omics resource melPDomiX maps gain- and loss-of-function alterations.Cell reports · 2026Article
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
- SNORD50A/B disassemble ASC-1 complex to silence NF-κB and boost PD-1 blockade in non-small-cell lung cancer.NPJ precision oncology · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Targeting NRF2 addiction in cancer: synthetic lethal strategies beyond direct inhibition.Frontiers in cell and developmental biology · 2026Review
- Tumor Genomic Profiles Associated with Clinical Benefit from Immune Checkpoint Inhibitor Therapy - An Exploratory Analysis of the INFINITY Precision Oncology Registry.OncoTargets and therapy · 2026Article
- Prognostic analysis and development of a prognostic model for EML4-ALK-positive lung cancer patients treated with ALK-TKIs.Frontiers in medicine · 2026Article
- Advances in Metabolic Reprogramming and Immune Regulatory Mechanisms in Lung Cancer.Oncology research · 2026Review
- Effects of the Pharmacological Modulation of NRF2 in Cancer Progression.Medicina (Kaunas, Lithuania) · 2025Review
- Loss of UXS1 Selectively Depletes Pyrimidines and Induces Replication Stress in KEAP1-Mutant Lung Cancer.Cancer research · 2025Article
- Druggable genome CRISPR screening identifies the KEAP1/NRF2 axis as a mediator of PD-L1 expression.Communications biology · 2025Article
- The influence of ferroptosis-associated gene HSPA5 on the prognosis and immune evasion of lung adenocarcinoma.Discover oncology · 2025Article
- Biochemical analysis of PD-L1 ubiquitination by CRL3Structure (London, England : 1993) · 2025Article
- Genetic drivers of tumor microenvironment and immunotherapy resistance in non-small cell lung cancer: the role ofJournal for immunotherapy of cancer · 2025Review
- Prognostic Impact of KRAS-TP53 Co-Mutations in Patients with Early-Stage Non-Small Cell Lung Cancer: A Single-Center Retrospective Study.Journal of clinical medicine · 2025Article
- Mechanistic Insights and Therapeutic Potentials of Ubiquitin-Proteasome System in Non-Small Cell Lung Cancer.Cell proliferation · 2025Review
- Article
- Tumor microenvironment regulation by reactive oxygen species-mediated inflammasome activation.Archives of pharmacal research · 2025Review
- Multi-omics analysis reveals glutathione metabolism-related immune suppression and constructs a prognostic model in lung adenocarcinoma.Frontiers in immunology · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Immunotherapy has become a prominent first-line cancer treatment strategy. In non-small cell lung cancer (NSCLC), the expression of PD-L1 induces an immuno-suppressive effect to protect cancer cells from immune elimination, which designates PD-L1 as an important target for immunotherapy. However, little is known about the regulation mechanism and the function of PD-L1 in lung cancer. In this study, we have discovered that KEAP1 serves as an E3 ligase to promote PD-L1 ubiquitination and degradation. We found that overexpression of KEAP1 suppressed tumor growth and promoted cytotoxic T-cell activation in vivo. These results indicate the important role of KEAP1 in anti-cancer immunity. Moreover, the combination of elevated KEAP1 expression with anti-PD-L1 immunotherapy resulted in a synergistic effect on both tumor growth and cytotoxic T-cell activation. Additionally, we found that the expressions of KEAP1 and PD-L1 were associated with NSCLC prognosis. In summary, our findings shed light on the mechanism of PD-L1 degradation and how NSCLC immune escape through KEAP1-PD-L1 signaling. Our results also suggest that KEAP1 agonist might be a potential clinical drug to boost anti-tumor immunity and improve immunotherapies in NSCLC.
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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.