ArticleJournal of immunology (Baltimore, Md. : 1950)2015
OX40- and CD27-mediated costimulation synergizes with anti-PD-L1 blockade by forcing exhausted CD8+ T cells to exit quiescence.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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
44 citing papers in PubMed, 78 citations in OpenAlex.
- Trial
- Oncolytic virus-mediated immunomodulation in glioblastoma: Insights from clinical trials and challenges.Seminars in immunology · 2025Review
- Multispecific Antibodies Targeting PD-1/PD-L1 in Cancer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Deciphering T-cell exhaustion in the tumor microenvironment: paving the way for innovative solid tumor therapies.Frontiers in immunology · 2025Review
- Leucine zipper-based immunomagnetic purification of CAR T cells displaying multiple receptors.Nature biomedical engineering · 2024Article
- Article
- Article
- Tumor-derived semaphorin 4A improves PD-1-blocking antibody efficacy by enhancing CD8Science advances · 2023Article
- Beyond CTLA-4 and PD-1 Inhibition: Novel Immune Checkpoint Molecules for Melanoma Treatment.Cancers · 2023Review
- CD70 and PD-L1 (CD274) co-expression predicts poor clinical outcomes in patients with pleural mesothelioma.The journal of pathology. Clinical research · 2023Article
- Total T Cell Density and Expression of T Memory Stem Cell Markers are Associated with Better Prognosis in Colon Cancer.International journal of general medicine · 2023Article
- Characteristics of tumor microenvironment and novel immunotherapeutic strategies for non-small cell lung cancer.Journal of the National Cancer Center · 2022Review
- Future Prospects of Immunotherapy in Non-Small-Cell Lung Cancer Patients: Is There Hope in Other Immune Checkpoints Targeting Molecules?International journal of molecular sciences · 2022Review
- Targeting TNFR2: A Novel Breakthrough in the Treatment of Cancer.Frontiers in oncology · 2022Review
- Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives.Cancers · 2021Review
- Attenuated activation of pulmonary immune cells in mRNA-1273-vaccinated hamsters after SARS-CoV-2 infection.The Journal of clinical investigation · 2021Article
- Two Complementarity Immunotherapeutics in Non-Small-Cell Lung Cancer Patients-Mechanism of Action and Future Concepts.Cancers · 2021Review
- Detection of differentially abundant cell subpopulations in scRNA-seq data.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors.Frontiers in cell and developmental biology · 2021Review
- Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy.Pharmaceutics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
Exhaustion of chronically stimulated CD8(+) T cells is a significant obstacle to immune control of chronic infections or tumors. Although coinhibitory checkpoint blockade with anti-programmed death ligand 1 (PD-L1) Ab can restore functions to exhausted T cell populations, recovery is often incomplete and dependent upon the pool size of a quiescent T-bet(high) subset that expresses lower levels of PD-1. In a model in which unhelped, HY-specific CD8(+) T cells gradually lose function following transfer to male bone marrow transplantation recipients, we have explored the effect of shifting the balance away from coinhibition and toward costimulation by combining anti-PD-L1 with agonistic Abs to the TNFR superfamily members, OX40 and CD27. Several weeks following T cell transfer, both agonistic Abs, but especially anti-CD27, demonstrated synergy with anti-PD-L1 by enhancing CD8(+) T cell proliferation and effector cytokine generation. Anti-CD27 and anti-PD-L1 synergized by downregulating the expression of multiple quiescence-related genes concomitant with a reduced frequency of T-bet(high) cells within the exhausted population. However, in the presence of persistent Ag, the CD8(+) T cell response was not sustained and the overall size of the effector cytokine-producing pool eventually contracted to levels below that of controls. Thus, CD27-mediated costimulation can synergize with coinhibitory checkpoint blockade to switch off molecular programs for quiescence in exhausted T cell populations, but at the expense of losing precursor cells required to maintain a response.
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.