ArticleOncogene2021
Repurposing screen identifies Amlodipine as an inducer of PD-L1 degradation and antitumor immunity.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 51 citations in OpenAlex.
- In silico screen identifies Pranidipine as a potential inhibitor of the PD-1/PD-L1 immune checkpoint.Scientific reports · 2026Article
- ROCK1 inhibition primes anti-tumor immunity in EGFR-mutant NSCLC by triggering PD-L1 degradation mediated by SMURF2.Molecular cancer · 2026Article
- Article
- Antihypertensive Drug Target Genes and Epithelial Ovarian Cancer Risk: A Two-Sample Mendelian Randomization Study.International journal of women's health · 2026Article
- Recent advances in drug repurposing for cancer immunomodulation emerging strategies, mechanistic insights, and clinical translation.Frontiers in oncology · 2026Review
- Amlodipine exerts inhibitory effects against glioma stem cells through degrading EGFR and down-regulating its downstream pro-survival pathways.Cell death discovery · 2025Article
- Programmed cell death in triple-negative breast cancer.Cellular & molecular biology letters · 2025Review
- Amlodipine with letrozole as maintenance post-chemotherapy: targeting calcium calcineurin calmodulin pathway and aromatase inhibitor in disseminated endometrioid adenocarcinoma of the endometrium-a case report.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Amlodipine as an immunomodulator to enhance dendritic cell activation in cancer therapy with tumor-associated antigens.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Extracellular Vesicles and PD-L1-A Review of Complex Immunoregulatory Properties and Clinical Importance.Biomedicines · 2025Review
- The Role of Ion Channels in Cervical Cancer Progression: From Molecular Biomarkers to Diagnostic and Therapeutic Innovations.Cancers · 2025Review
- Metal-modulated T cell antitumor immunity and emerging metalloimmunotherapy.Cancer metastasis reviews · 2025Review
- Amlodipine, an L-type Ca2+ channel inhibitor, regulates release of extracellular vesicles from tumor cells.Carcinogenesis · 2025Article
- Autophagy in tumor immune escape and immunotherapy.Molecular cancer · 2025Review
- A cohort-based multi-omics identifies nuclear translocation of eIF5B /PD-L1/CD44 complex as the target to overcome Osimertinib resistance of ARID1A-deficient lung adenocarcinoma.Experimental hematology & oncology · 2025Article
- Metabolomic Analysis, Antiproliferative, Anti-Migratory, and Anti-Invasive Potential of Amlodipine in Lung Cancer Cells.Drug design, development and therapy · 2025Article
- Zosuquidar Promotes Antitumor Immunity by Inducing Autophagic Degradation of PD-L1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Autologous patient-derived exhausted nano T-cells exploit tumor immune evasion to engage an effective cancer therapy.Molecular cancer · 2024Article
- Beyond inhibition against the PD-1/PD-L1 pathway: development of PD-L1 inhibitors targeting internalization and degradation of PD-L1.RSC medicinal chemistry · 2024Review
- Challenges Coexist with Opportunities: Spatial Heterogeneity Expression of PD-L1 in Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cell expression of PD-L1 leads to T cells exhaustion by transducing co-inhibitory signal, and further understanding the regulation of PD-L1 in cancer cells may provide additional therapeutic strategies. Here by drug repurposing screen, we identified amlodipine as a potent inhibitor of PD-L1 expression in cancer cells. Further survey of calcium-associated pathways revealed calpain-dependent stabilization of the PD-L1 protein. Intracellular calcium delivered an operational signal to calpain-dependent Beclin-1 cleavage, blocking autophagic degradation of PD-L1 accumulated on recycling endosome (RE). Blocking calcium flux by amlodipine depleted PD-L1 expression and increased CD8+ T-cell infiltration in tumor tissues but not in myocardium, causing dose-dependent tumor suppression in vivo. Rescuing PD-L1 expression eliminated the effects of amlodipine, suggesting the PD-L1-dependent effect of amlodipine. These results reveal a calcium-dependent mechanism controlling PD-L1 degradation, and highlight calcium flux blockade as a potential strategy for combinatorial immunotherapy.
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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.