ArticleProceedings of the National Academy of Sciences of the United States of America2018
Affinity purification mass spectrometry analysis of PD-1 uncovers SAP as a new checkpoint inhibitor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Efficacy of neoadjuvant PD-1/PD-L1 inhibitor in resectable NSCLC: a meta-analysis based on randomized controlled trials.BMC cancer · 2024Pooled it
- Understanding the Therapeutic Potential of PD-1 Agonism in Inflammatory and Autoimmune Disorders.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Article
- PD-1 protects expanding human T cells from premature restimulation-induced cell death by modulating TCR and CD28 signaling.Cell death & disease · 2026Article
- X-linked lymphoproliferative disease type 1: a clinical and genetic update.Frontiers in immunology · 2025Review
- Changing the location of proteins on the cell surface is a promising strategy for modulating T cell functions.Immunology · 2024Review
- Exclusion of PD-1 from the immune synapse: A novel strategy to modulate T cell function.Molecular therapy. Oncology · 2024Article
- Proteomic Investigation of Immune Checkpoints and Some of Their Inhibitors.International journal of molecular sciences · 2024Review
- In vitro T cell responses to PD-1 blockade are reduced by IFN-α but do not predict therapy response in melanoma patients.Cancer immunology, immunotherapy : CII · 2024Article
- Proteomics from compartment-specific APEX2 labeling in Mycobacterium tuberculosis reveals Type VII secretion substrates in the cell wall.Cell chemical biology · 2024Article
- Experiment-guided molecular simulations define a heterogeneous structural ensemble for theChemical science · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapy.Frontiers in immunology · 2023Review
- Small molecule inhibitors for cancer immunotherapy and associated biomarkers - the current status.Frontiers in immunology · 2023Review
- SLAM-family receptors come of age as a potential molecular target in cancer immunotherapy.Frontiers in immunology · 2023Review
- Wiskott-Aldrich syndrome protein interacts and inhibits diacylglycerol kinase alpha promoting IL-2 induction.Frontiers in immunology · 2023Article
- Immune Checkpoint Receptors Signaling in T Cells.International journal of molecular sciences · 2022Review
- Quantifying the contribution of transcription factor activity, mutations and microRNAs to CD274 expression in cancer patients.Scientific reports · 2022Article
- Cryo-EM structures reveal high-resolution mechanism of a DNA polymerase sliding clamp loader.eLife · 2022Article
- Combination Approaches to Target PD-1 Signaling in Cancer.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Programmed cell death-1 (PD-1) is an essential inhibitory receptor in T cells. Antibodies targeting PD-1 elicit durable clinical responses in patients with multiple tumor indications. Nevertheless, a significant proportion of patients do not respond to anti-PD-1 treatment, and a better understanding of the signaling pathways downstream of PD-1 could provide biomarkers for those whose tumors respond and new therapeutic approaches for those whose tumors do not. We used affinity purification mass spectrometry to uncover multiple proteins associated with PD-1. Among these proteins, signaling lymphocytic activation molecule-associated protein (SAP) was functionally and mechanistically analyzed for its contribution to PD-1 inhibitory responses. Silencing of SAP augmented and overexpression blocked PD-1 function. T cells from patients with X-linked lymphoproliferative disease (XLP), who lack functional SAP, were hyperresponsive to PD-1 signaling, confirming its inhibitory role downstream of PD-1. Strikingly, signaling downstream of PD-1 in purified T cell subsets did not correlate with PD-1 surface expression but was inversely correlated with intracellular SAP levels. Mechanistically, SAP opposed PD-1 function by acting as a molecular shield of key tyrosine residues that are targets for the tyrosine phosphatase SHP2, which mediates PD-1 inhibitory properties. Our results identify SAP as an inhibitor of PD-1 function and SHP2 as a potential therapeutic target in patients with XLP.
Indexed as
Identifiers
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.