ArticleCell communication and signaling : CCS2023
Proximity proteome mapping reveals PD-L1-dependent pathways disrupted by anti-PD-L1 antibody specifically in EGFR-mutant lung cancer cells.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma.Molecular oncology · 2026Article
- Tumor cell intrinsic mechanisms of immune escape.Cell communication and signaling : CCS · 2026Review
- ANCA-negative pauci-immune crescentic glomerulonephritis associated with nivolumab in lung cancer.CEN case reports · 2026Article
- Intracellular PD-L1: Functions, Regulation, and Therapeutic Implications.International journal of biological sciences · 2026Review
- Targeting PD-L1-CMTM6 interactions in myeloid cells triggers PD-L1 degradation and enhances cytotoxic T-cell expansion.Journal for immunotherapy of cancer · 2025Article
- Investigating the correlation between IDO1/PD-L1 expression or co-expression and EGFR/KRAS gene mutations in advanced NSCLC.Scientific reports · 2025Article
- Resetting the Hsc70-mediated lysosomal degradation of PD-L1 via a supramolecular meso peptide for the restoration of acquired anti-tumor T cell immunity.Journal of nanobiotechnology · 2025Article
- Polygonatum polysaccharides as gut microbiota modulators: implications for autophagy-dependent PD-L1 clearance in cancer immunotherapy.Frontiers in nutrition · 2025Review
- DRG2 as a Biomarker to Enhance the Predictive Efficacy of PD-L1 Immunohistochemistry Assays.Biomedicines · 2024Article
- Hsc70 promotes anti-tumor immunity by targeting PD-L1 for lysosomal degradation.Nature communications · 2024Article
- Regulation of PD-L1 Trafficking from Synthesis to Degradation.Cancer immunology research · 2023Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPD-L1, a transmembrane ligand for immune checkpoint receptor PD1, has been successfully targeted to activate an anti-tumor immune response in a variety of solid tumors, including non-small cell lung cancer (NSCLC). Despite the success of targeting PD-L1, only about 20% of patients achieve a durable response. The reasons for the heterogeneity in response are not understood, although some molecular subtypes (e.g., mutant EGF receptor tumors) are generally poor responders. Although PD-L1 is best characterized as a transmembrane PD1 ligand, the emerging view is that PD-L1 has functions independent of activating PD1 signaling. It is not known whether these cell-intrinsic functions of PD-L1 are shared among non-transformed and transformed cells, if they vary among cancer molecular subtypes, or if they are impacted by anti-PD-L1 therapy.
methodsHere we use quantitative microscopy techniques and APEX2 proximity mapping to describe the behavior of PD-L1 and to identify PD-L1's proximal proteome in human lung epithelial cells.
resultsOur data reveal growth factor control of PD-L1 recycling as a mechanism for acute and reversible regulation of PD-L1 density on the plasma membrane. In addition, we describe novel PD-L1 biology restricted to mutant EGFR cells. Anti-PD-L1 antibody treatment of mutant EGFR cells perturbs cell intrinsic PD-L1 functions, leading to reduced cell migration, increased half-life of EGFR and increased extracellular vesicle biogenesis, whereas anti-PD-L1 antibody does not induce these changes in wild type EGFR cells.
conclusionsGrowth factor acute regulation of PD-L1 trafficking, by contributing to the control of plasma membrane density, might contribute to the regulation of PD-L1's immune checkpoint activity, whereas the specific effects of anti-PD-L1 on mutant EGFR cells might contribute to the poor anti-PD-L1 response of mutant EGFR tumors. Video Abstract.
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