Observational studyThe Journal of clinical investigation2024
Soluble immune checkpoint factors reflect exhaustion of antitumor immunity and response to PD-1 blockade.
Observational study in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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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
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Soluble immune checkpoints in lung cancer: linking prognostic signatures to immunotherapy response - a meta-analysis.Frontiers in immunology · 2026Pooled it
- Guiding the Application of Immunotherapy in Nonsmall Cell Lung Cancer: The Role of Biomarkers.Thoracic cancer · 2026Review
- Emotional distress and clinical response to neoadjuvant chemoimmunotherapy in resectable non-small-cell lung cancer: a protocol for the prospective observational NeoFUSE-Lung cohort study.Translational lung cancer research · 2026Article
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Glycosylation-related gene risk model and functional validation of OSTC and TUBA1C in lung adenocarcinoma.Respiratory research · 2026Article
- Soluble Immune Checkpoints as Prognostic Biomarkers in Small Cell Lung Cancer Patients Treated with Chemotherapy and Anti-PD-L1.International journal of molecular sciences · 2026Article
- A Circulating GPNMB-Based Multimodal Model Integrates Tumor-Immune Crosstalk to Predict Immunotherapy Response in Esophageal Cancer.Cancer discovery · 2026Article
- Core regulatory mechanisms of the PD-L1 axis and clinical strategies for immune escape and immunotherapy response in nasopharyngeal carcinoma.Translational oncology · 2026Review
- Peripheral Blood Biomarkers Predict Outcomes in Advanced Cancers Treated With Anti-PD-1 Therapy.Immunity, inflammation and disease · 2026Article
- PARP inhibitors restore NK cell function via secretory crosstalk with tumor cells in prostate cancer.The Journal of clinical investigation · 2026Article
- Mesothelin biology and the evolving landscape of targeted immunotherapy.Molecular therapy. Oncology · 2026Review
- Review
- PD-1, BTLA and TIGIT as therapeutic targets for rheumatic disease.Nature reviews. Rheumatology · 2026Review
- Depletion of Soluble PD-L1 with Engineered Nanoparticles Promotes Antitumor Immunity and Tumor Control.International journal of nanomedicine · 2026Article
- Soluble CTLA-4 as a context-dependent immune checkpoint: biology, biomarker potential, and therapeutic implications.Frontiers in immunology · 2026Review
- Targeting ubiquitin-specific peptidase 22 in solid tumours: from ubiquitination to immunotherapy.Frontiers in cell and developmental biology · 2026Review
- A multiplexed assay by self-assembled dual-target responsive DNA hydrogels for efficacy evaluation of immunotherapy.Nature communications · 2025Article
- Modified epitope peptides targeting the porcine PD-1/PD-L1 interaction enhance cellular and humoral immune responses.Journal of veterinary science · 2025Article
- Overcoming resistance to anti-PD-L1 immunotherapy: mechanisms, combination strategies, and future directions.Molecular cancer · 2025Review
- Update on the Treatment of Non-Small Cell Lung Carcinoma (NSCLC).Journal of clinical medicine · 2025Review
Corrections and comments
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Authors and funding
29 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUNDPrecise stratification of patients with non-small cell lung cancer (NSCLC) is needed for appropriate application of PD-1/PD-L1 blockade therapy.METHODSWe measured soluble forms of the immune-checkpoint molecules PD-L1, PD-1, and CTLA-4 in plasma of patients with advanced NSCLC before PD-1/PD-L1 blockade. A prospective biomarker-finding trial (cohort A) included 50 previously treated patients who received nivolumab. A retrospective observational study was performed for patients treated with any PD-1/PD-L1 blockade therapy (cohorts B and C), cytotoxic chemotherapy (cohort D), or targeted therapy (cohort E). Plasma samples from all patients were assayed for soluble immune-checkpoint molecules with a highly sensitive chemiluminescence-based assay.RESULTSNonresponsiveness to PD-1/PD-L1 blockade therapy was associated with higher concentrations of these soluble immune factors among patients with immune-reactive (hot) tumors. Such an association was not apparent for patients treated with cytotoxic chemotherapy or targeted therapy. Integrative analysis of tumor size, PD-L1 expression in tumor tissue (tPD-L1), and gene expression in tumor tissue and peripheral CD8+ T cells revealed that high concentrations of the 3 soluble immune factors were associated with hyper or terminal exhaustion of antitumor immunity. The combination of soluble PD-L1 (sPD-L1) and sCTLA-4 efficiently discriminated responsiveness to PD-1/PD-L1 blockade among patients with immune-reactive tumors.CONCLUSIONCombinations of soluble immune factors might be able to identify patients unlikely to respond to PD-1/PD-L1 blockade as a result of terminal exhaustion of antitumor immunity. Our data suggest that such a combination better predicts, along with tPD-L1, for the response of patients with NSCLC.TRIAL REGISTRATIONUMIN000019674.FUNDINGThis study was funded by Ono Pharmaceutical Co. Ltd. and Sysmex Corporation.
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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.