ArticleBlood advances2018
Soluble PD-1 ligands regulate T-cell function in Waldenstrom macroglobulinemia.
Article in Blood advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Prognostic and clinicopathological role of soluble programmed cell death ligand-1 in patients with diffuse large B-cell lymphoma: a meta-analysis.Frontiers in oncology · 2025Pooled it
- Prognostic value of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) for hepatocellular carcinoma: a systematic review and meta-analysis.Cancer immunology, immunotherapy : CII · 2022Pooled it
- Soluble Immune Checkpoints and Anti-HLA Antibodies in Kidney Transplant Recipients: Associations With Kidney Function.Immunology · 2026Article
- Uncovering regulatory B-cell features associated with regulatory T-cell expansion and global T-cell exhaustion in Waldenström macroglobulinemiaHemaSphere · 2025Article
- Single-cell RNA sequencing defines distinct disease subtypes and reveals hypo-responsiveness to interferon in asymptomatic Waldenstrom's Macroglobulinemia.Nature communications · 2025Article
- Genomic and immune profiling of prognostic risk groups in IgM gammopathy reveals novel biomarkers beyondFrontiers in immunology · 2025Article
- GLI3 Is Required for M2 Macrophage Polarization and M2-Mediated Waldenström Macroglobulinemia Growth and Survival.International journal of molecular sciences · 2024Article
- PD-L1 and PD-1 Are Associated with Clinical Outcomes and Alveolar Immune Cell Activation in Acute Respiratory Distress Syndrome.American journal of respiratory cell and molecular biology · 2024Article
- Waldenström Macroglobulinemia - A State-of-the-Art Review: Part 1: Epidemiology, Pathogenesis, Clinicopathologic Characteristics, Differential Diagnosis, Risk Stratification, and Clinical Problems.Mediterranean journal of hematology and infectious diseases · 2024Review
- Dysfunctions of innate and adaptive immune tumor microenvironment in Waldenström macroglobulinemia.International journal of cancer · 2023Article
- Long Non-Coding RNAs as Epigenetic Regulators of Immune Checkpoints in Cancer Immunity.Cancers · 2022Review
- Single-cell profiles reveal tumor cell heterogeneity and immunosuppressive microenvironment in Waldenström macroglobulinemia.Journal of translational medicine · 2022Article
- Waldenström Macroglobulinemia: Mechanisms of Disease Progression and Current Therapies.International journal of molecular sciences · 2022Review
- CXCL10 and Soluble Programmed Death-Ligand 1 during Respiratory Viral Infections Are Associated with Chronic Lung Allograft Dysfunction in Lung Transplant Recipients.American journal of respiratory cell and molecular biology · 2022Article
- Adenosinergic axis and immune checkpoint combination therapy in tumor: A new perspective for immunotherapy strategy.Frontiers in immunology · 2022Review
- The Programmed Death-1 Pathway Counter-Regulates Inflammation-Induced Osteoclast Activity in Clinical and Experimental Settings.Frontiers in immunology · 2022Article
- Aberrant Extrafollicular B Cells, Immune Dysfunction, Myeloid Inflammation, and MyD88-Mutant Progenitors Precede Waldenstrom Macroglobulinemia.Blood cancer discovery · 2021Article
- Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases.Cancers · 2021Review
- Circulating low CD4Annals of hematology · 2021Article
- Checkpoint Molecules in Rheumatology-or the Benefits of Being Exhausted.Current rheumatology reports · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Although immune checkpoint molecules regulate the progression of certain cancers, their significance in malignant development of Waldenstrom macroglobulinemia (WM), an incurable low-grade B-cell lymphoma, remains unknown. Recently, cytokines in the bone marrow (BM) microenvironment are shown to contribute to the pathobiology of WM. Here, we investigated the impact of cytokines, including interleukin-6 (IL-6) and IL-21, on immune regulation and particularly on the programmed death-1 (PD-1) and its ligands PD-L1 and PD-L2. We showed that IL-21, interferon γ, and IL-6 significantly induced PD-L1 and PD-L2 gene expression in WM cell lines. Increased PD-L1 and PD-L2 messenger RNA was also detected in patients' BM cells. Patients' nonmalignant BM cells, including T cells and monocytes, showed increased PD-L1, but minimal or undetectable PD-L2 surface expression. There was also very modest PD-L1 and PD-L2 surface expression by malignant WM cells, suggesting that ligands are cleaved from the cell surface. Levels of soluble ligands were higher in patients' BM plasma and blood serum than controls. Furthermore, IL-21 and IL-6 increased secreted PD-L1 in the culture media of WM cell lines, implying that elevated levels of soluble PD-1 ligands are cytokine mediated. Soluble PD-1 ligands reduced T-cell proliferation, phosphorylated extracellular signal-regulated kinase and cyclin A levels, mitochondrial adenosine triphosphate production, and spare respiratory capacity. In conclusion, we identify that soluble PD-1 ligands are elevated in WM patients and, in addition to surface-bound ligands in WM BM, could regulate T-cell function. Given the capability of secreted forms to be bioactive at distant sites, soluble PD-1 ligands have the potential to promote disease progression in WM.
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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.