ArticleJournal of the National Cancer Institute2016
PDL1 Regulation by p53 via miR-34.
Article in Journal of the National Cancer Institute, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 432 papers, 2 of them syntheses that pooled it.
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Who cites it
432 citing papers in PubMed, 2 syntheses or guidelines pooled it, 664 citations in OpenAlex.
- Influence ofJCO precision oncology · 2024Pooled it
- The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy.International journal of molecular sciences · 2022Pooled it
- Trial
- Effect Evaluation of Bronchial Artery Embolization for Hemoptysis of Lung Cancer and Changes in Serum Tumor Markers and miR-34 Levels.Contrast media & molecular imaging · 2022Trial
- Circulating MicroRNAs in non-small cell lung cancer: Clinical potential, analytic pitfalls, and barriers to implementation.The journal of liquid biopsy · 2026Review
- The Role of PD-L1 in Treatment Decision-Making for Perioperative EGFR-Mutated Lung Cancer and its Genomic Analysis.Annals of surgical oncology · 2026Article
- ClonalLife science alliance · 2026Article
- microRNAs as Regulators of the Immune Response and Their Potential Therapeutic Applications in Cancer.Non-coding RNA · 2026Review
- Revisiting tumor immunogenicity through the lens of mutant p53: Implications for cancer immunotherapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Clinical significance of miRNAs and exosomal miRNAs in non-small cell lung cancer: diagnostic, prognostic, and therapeutic perspectives.Journal of human genetics · 2026Review
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Advances in miRNA-Mediated Bidirectional Crosstalk and Immune Evasion Mechanisms Between Lung Cancer Cells and CD8International journal of molecular sciences · 2026Review
- Targeting Immune Checkpoint Proteins in Cancer Therapy and the Potential of RNAi-Based Immunotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Comprehensive Review of the Interplay of MicroRNA and Epithelial-Mesenchymal Transition in Radiation Resistance of Cancer.International journal of molecular sciences · 2026Review
- Emerging role of microRNAs as modulators of the tumor immune microenvironment.Journal for immunotherapy of cancer · 2026Review
- TP53 mutation is associated with improved disease control in patients with advanced RAS wild-type colorectal adenocarcinoma treated with cetuximab and pembrolizumab.International journal of cancer · 2026Article
- mTOR inhibition augments antitumor immune effector response by reprogramming thebioRxiv : the preprint server for biology · 2026Article
- Targeting p53 in Cancer: Functional States, Therapeutic Strategies, and Clinical Progress.Cancers · 2026Review
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
372 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAlthough clinical studies have shown promise for targeting PD1/PDL1 signaling in non-small cell lung cancer (NSCLC), the regulation of PDL1 expression is poorly understood. Here, we show that PDL1 is regulated by p53 via miR-34.
methodsp53 wild-type and p53-deficient cell lines (p53(-/-) and p53(+/+) HCT116, p53-inducible H1299, and p53-knockdown H460) were used to determine if p53 regulates PDL1 via miR-34. PDL1 and miR-34a expression were analyzed in samples from patients with NSCLC and mutated p53 vs wild-type p53 tumors from The Cancer Genome Atlas for Lung Adenocarcinoma (TCGA LUAD). We confirmed that PDL1 is a direct target of miR-34 with western blotting and luciferase assays and used a p53(R172HΔ)g/+K-ras(LA1/+) syngeneic mouse model (n = 12) to deliver miR-34a-loaded liposomes (MRX34) plus radiotherapy (XRT) and assessed PDL1 expression and tumor-infiltrating lymphocytes (TILs). A two-sided t test was applied to compare the mean between different treatments.
resultsWe found that p53 regulates PDL1 via miR-34, which directly binds to the PDL1 3' untranslated region in models of NSCLC (fold-change luciferase activity to control group, mean for miR-34a = 0.50, SD = 0.2, P < .001; mean for miR-34b = 0.52, SD = 0.2, P = .006; and mean for miR-34c = 0.59, SD = 0.14, and P = .006). Therapeutic delivery of MRX34, currently the subject of a phase I clinical trial, promoted TILs (mean of CD8 expression percentage of control group = 22.5%, SD = 1.9%; mean of CD8 expression percentage of MRX34 = 30.1%, SD = 3.7%, P = .016, n = 4) and reduced CD8(+)PD1(+) cells in vivo (mean of CD8/PD1 expression percentage of control group = 40.2%, SD = 6.2%; mean of CD8/PD1 expression percentage of MRX34 = 20.3%, SD = 5.1%, P = .001, n = 4). Further, MRX34 plus XRT increased CD8(+) cell numbers more than either therapy alone (mean of CD8 expression percentage of MRX34 plus XRT to control group = 44.2%, SD = 8.7%, P = .004, n = 4). Finally, miR-34a delivery reduced the numbers of radiation-induced macrophages (mean of F4-80 expression percentage of control group = 52.4%, SD = 1.7%; mean of F4-80 expression percentage of MRX34 = 40.1%, SD = 3.5%, P = .008, n = 4) and T-regulatory cells.
conclusionsWe identified a novel mechanism by which tumor immune evasion is regulated by p53/miR-34/PDL1 axis. Our results suggest that delivery of miRNAs with standard therapies, such as XRT, may represent a novel therapeutic approach for lung cancer.
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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.