ArticleImmunity2019
PD-L1:CD80 Cis-Heterodimer Triggers the Co-stimulatory Receptor CD28 While Repressing the Inhibitory PD-1 and CTLA-4 Pathways.
Article in Immunity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 234 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.
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
234 citing papers in PubMed, 381 citations in OpenAlex.
- Safety and efficacy of first-line iparomlimab and tuvonralimab (QL1706) plus carboplatin and etoposide in patients with extensive-stage small cell lung cancer: an open-label, single-arm, phase 2 trial (DUBHE-L-209).Frontiers in immunology · 2026Trial
- Atezolizumab, obinutuzumab and venetoclax for the treatment of patients with relapsed/refractory B non-Hodgkin lymphoma: Final analysis of a phase II trial from the LYSA group.British journal of haematology · 2025Trial
- Incidence of and risk factors for immune checkpoint inhibitor-related pneumonitis in thoracic malignancies: a prospective multicenter study.The oncologist · 2026Observational
- Engineered CTLA-4 targeting chimeras for targeted protein degradation and immune synapse reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Risk of Neurological Adverse Events Between PD-L1 and PD-1 Inhibitors in South Korean Patients with Lung Cancer: A Target Trial Emulation Framework.Clinical drug investigation · 2026Article
- CD80 as an Important Immune Mediator and Therapeutic Target in Atherosclerosis.International journal of molecular sciences · 2026Review
- Phagocytosis of necroptotic cells optimizes type 1 conventional dendritic cells for induction of a cytotoxic T-cell response.Cell death and differentiation · 2026Article
- Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells.Nature biotechnology · 2026Article
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- PD-L1 deletion or blockade regulate macrophage antigen presentation and checkpoint molecule surface levels.bioRxiv : the preprint server for biology · 2026Article
- Studying Macromolecular Composition in Cell-Cell Interfaces Using 3D Membrane Reconstitution Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ALG1-mediated PDL1 glycosylation drives macrophage m2 polarization to promote bladder cancer progression.Cell death and differentiation · 2026Article
- Immune Checkpoint-Based Therapies in Colorectal Cancer-Current Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- Review
- Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma.Molecular oncology · 2026Article
- Review
- Mechanical force regulates the inhibitory function of PD-1.EMBO reports · 2026Article
- Mesenchymal Stromal Cells Respond to SARS-CoV-2 Peptides and Exhibit Altered T-Cell Regulatory Capacity.Cells · 2026Article
- PD1-induced Shp2 condensation organizes inhibitory signalosomes through selective substrate partitioning.bioRxiv : the preprint server for biology · 2026Article
- PD-L1 cell-intrinsic signals limit immune activation during cutaneous vaccinia virus infection.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
174 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Combined immunotherapy targeting the immune checkpoint receptors cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1), or CTLA-4 and the PD-1 ligand (PD-L1) exhibits superior anti-tumor responses compared with single-agent therapy. Here, we examined the molecular basis for this synergy. Using reconstitution assays with fluorescence readouts, we found that PD-L1 and the CTLA-4 ligand CD80 heterodimerize in cis but not trans. Quantitative biochemistry and cell biology assays revealed that PD-L1:CD80 cis-heterodimerization inhibited both PD-L1:PD-1 and CD80:CTLA-4 interactions through distinct mechanisms but preserved the ability of CD80 to activate the T cell co-stimulatory receptor CD28. Furthermore, PD-L1 expression on antigen-presenting cells (APCs) prevented CTLA-4-mediated trans-endocytosis of CD80. Atezolizumab (anti-PD-L1), but not anti-PD-1, reduced cell surface expression of CD80 on APCs, and this effect was negated by co-blockade of CTLA-4 with ipilimumab (anti-CTLA-4). Thus, PD-L1 exerts an immunostimulatory effect by repressing the CTLA-4 axis; this has implications to the synergy of anti-PD-L1 and anti-CTLA-4 combination therapy.
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What OpenQuestion holds
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.