ArticleCell reports2021
PD-L1 recruits phospholipase C and enhances tumorigenicity of lung tumors harboring mutant forms of EGFR.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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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
22 citing papers in PubMed, 44 citations in OpenAlex.
- EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Sensitizing Immune-Refractory Ovarian Tumors via p53 Mutation-Tailored Immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Programmed Death-1 Ligand 1 Domain Organization, Signaling Motifs, and Interactors in Cancer Immunotherapy.Cancers · 2025Review
- Article
- PD-L1 expression in PitNETs: Correlations with the 2022 WHO classification.Brain & spine · 2025Article
- The roles of PD-L1 in the various stages of tumor metastasis.Cancer metastasis reviews · 2024Review
- CRISPR/Cas-Mediated Knockdown of PD-L1 and KRAS in Lung Cancer Cells.International journal of molecular sciences · 2024Article
- Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk.The FEBS journal · 2024Review
- Article
- Phospholipase Family Enzymes in Lung Cancer: Looking for Novel Therapeutic Approaches.Cancers · 2023Review
- Proximity proteome mapping reveals PD-L1-dependent pathways disrupted by anti-PD-L1 antibody specifically in EGFR-mutant lung cancer cells.Cell communication and signaling : CCS · 2023Article
- Pharmacological tumor PDL1 depletion with chlorambucil treats ovarian cancer and melanoma: improves antitumor immunity and renders anti-PDL1-resistant tumors anti-PDL1-sensitive through NK cell effects.Journal for immunotherapy of cancer · 2023Article
- Immune checkpoint receptors in autoimmunity.Current opinion in immunology · 2023Review
- Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy.Frontiers in oncology · 2023Review
- Bidirectional crosstalk between epithelial-mesenchymal plasticity and IFNRoyal Society open science · 2022Article
- Beyond Cancer: Regulation and Function of PD-L1 in Health and Immune-Related Diseases.International journal of molecular sciences · 2022Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Quantifying the contribution of transcription factor activity, mutations and microRNAs to CD274 expression in cancer patients.Scientific reports · 2022Article
- PD-L1 Mediates IFNγ-Regulation of Glucose but Not of Tryptophan Metabolism in Clear Cell Renal Cell Carcinoma.Frontiers in oncology · 2022Article
- Emerging Role of EGFR Mutations in Creating an Immune Suppressive Tumour Microenvironment.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
Abstract
Cancer immunotherapy focuses on inhibitors of checkpoint proteins, such as programmed death ligand 1 (PD-L1). Unlike RAS-mutated lung cancers, EGFR mutant tumors have a generally low response to immunotherapy. Because treatment outcomes vary by EGFR allele, intrinsic and microenvironmental factors may be involved. Among all non-immunological signaling pathways surveyed in patients' datasets, EGFR signaling is best associated with high PD-L1. Correspondingly, active EGFRs stabilize PD-L1 transcripts and depletion of PD-L1 severely inhibits EGFR-driven tumorigenicity and metastasis in mice. The underlying mechanisms involve the recruitment of phospholipase C-γ1 (PLC-γ1) to a cytoplasmic motif of PD-L1, which enhances PLC-γ1 activation by EGFR. Once stimulated, PLC-γ1 activates calcium flux, Rho GTPases, and protein kinase C, collectively promoting an aggressive phenotype. Anti-PD-L1 antibodies can inhibit these intrinsic functions of PD-L1. Our results portray PD-L1 as a molecular amplifier of EGFR signaling and improve the understanding of the resistance of EGFR
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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.