ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Neutralization of PD-L2 is Essential for Overcoming Immune Checkpoint Blockade Resistance in Ovarian Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- The efficacy and safety of neoadjuvant immunochemotherapy in resectable stage I-III non-small cell lung cancer: a systematic review and network meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Pooled it
- Spatial proteomics deciphers the immune niche landscape of non-ampullary duodenal adenocarcinoma.British journal of cancer · 2026Article
- Dendritic cell PD-L2 restrains intratumoral CD8bioRxiv : the preprint server for biology · 2026Article
- Tumour immune contexture and immune evasion in sporadic and Lynch syndrome-associated microsatellite unstable colorectal cancers.British journal of cancer · 2026Article
- Dual blockades of TIM-3 and PD-1 effectively prevent hyper-progression and enhance the efficacy of anti-PD-1 therapy in high-grade serous ovarian cancer.Cell death & disease · 2025Article
- Novel oncolytic adenovirus-based PEPvIII vaccine displays a super antitumor effect in glioma models.Journal for immunotherapy of cancer · 2025Article
- Decoding the immune landscape in Ewing sarcoma pathogenesis: The role of tumor infiltrating immune cells and immune milieu.Journal of bone oncology · 2025Review
- Dynamic Change of PD-L2 on Circulating Plasma Extracellular Vesicles as a Predictor of Treatment Response in Melanoma Patients Receiving Anti-PD-1 Therapy.Journal of extracellular vesicles · 2025Article
- Article
- Exploring correlations between gut mycobiome and lymphocytes in melanoma patients undergoing anti-PD-1 therapy.Cancer immunology, immunotherapy : CII · 2025Article
- Immune evasion in ovarian cancer: implications for immunotherapy and emerging treatments.Trends in immunology · 2025Review
- Article
- Beyond monoclonal antibodies: constraints and the case for alternative PD-1/PD-L1-targeting formats.Frontiers in immunology · 2025Review
- Review
- Soluble immune checkpoint molecules in cancer risk, outcomes prediction, and therapeutic applications.Biomarker research · 2024Review
- PD-L2 drives resistance to EGFR-TKIs: dynamic changes of the tumor immune environment and targeted therapy.Cell death and differentiation · 2024Article
- PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade.Cell biology and toxicology · 2024Article
- Article
- Cisplatin in the era of PARP inhibitors and immunotherapy.Pharmacology & therapeutics · 2024Review
- Let-7i enhances anti-tumour immunity and suppresses ovarian tumour growth.Cancer immunology, immunotherapy : CII · 2024Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
purposeOvarian cancer represents a major clinical hurdle for immune checkpoint blockade (ICB), with reported low patient response rates. We found that the immune checkpoint ligand PD-L2 is robustly expressed in patient samples of ovarian cancers and other malignancies exhibiting suboptimal response to ICB but not in cancers that are ICB sensitive. Therefore, we hypothesize that PD-L2 can facilitate immune escape from ICB through incomplete blockade of the PD-1 signaling pathway. EXPERIMENTAL
designWe engineered a soluble form of the PD-1 receptor (sPD-1) capable of binding and neutralizing both PD-L2 and PD-L1 with ×200 and ×10,000 folds improvement in binding affinity over wild-type PD-1 leading to superior inhibition of ligand-mediated PD-1 activities.
resultsBoth
conclusionsThe data presented in this study provide justification for using a dual targeting, high-affinity sPD-1 receptor as an alternative to PD-1 or PD-L1 therapeutic antibodies for achieving superior therapeutic efficacy in cancers expressing both PD-L2 and PD-L1.
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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.