ArticleScience (New York, N.Y.)2017
Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent.
Article in Science (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04262687 (Pembrolizumab in Combination With Xelox Bevacizumab in Patients With Microsatellite Stable Mestatic Colorectal Cancer and a High Immune Infiltrate), which is not on this map. Cited by 615 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.
Pembrolizumab in Combination With Xelox Bevacizumab in Patients With Microsatellite Stable Mestatic Colorectal Cancer and a High Immune Infiltrate : a Proof of Concept Study
Who cites it
615 citing papers in PubMed, 1 synthesis or guideline pooled it, 987 citations in OpenAlex.
- Efficacy and safety of PD-1/PD-L1 inhibitors in advanced or recurrent endometrial cancer: a meta-analysis with trial sequential analysis of randomized controlled trials.Frontiers in immunology · 2025Pooled it
- Immunological effects of supervised exercise in long COVID in adults: A secondary analysis of a randomized crossover trial.Physiological reports · 2026Trial
- Trial
- Toripalimab combined with definitive chemoradiotherapy for locally advanced cervical squamous cell carcinoma patients (TRACE): A single-arm, phase I/II trial.Cancer immunology, immunotherapy : CII · 2024Trial
- Blockade of LAG-3 and PD-1 leads to co-expression of cytotoxic and exhaustion gene modules in CD8Cell · 2024Trial
- Article
- Advanced gene editing technologies for oncology mechanisms, applications, and clinical implementation.Cancer gene therapy · 2026Review
- Multiscale modeling of T cell exhaustion: A mathematical framework integrating continuous dynamics with spatial heterogeneity.PLoS computational biology · 2026Article
- Co-stimulatory signal deficiency impairs cytotoxic T lymphocyte function in tumor immune evasion: molecular mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- MiR-139 modulates CD8iScience · 2026Article
- CD86 in Dendritic Cell-Mediated Cancer Immunity: From Maturation Marker to Functional Regulator.Biomedicines · 2026Review
- Immunological Significance of the ICI-PIT-ICI Sequence in Recurrent Oral Cancer: A Narrative Review with Illustrative Cases.Diagnostics (Basel, Switzerland) · 2026Review
- PD-1/PD-L1 Expression Could Be a Prognostic Factor in Patients with Acute Myeloid Leukemia.The Eurasian journal of medicine · 2026Article
- Exploring the landscape of programmed cell death protein-1 and cluster of differentiation 28 positive T cells and cytokines in non-small cell lung cancer: A retrospective case-control study.The Journal of international medical research · 2026Article
- New insights into progenitor exhausted T cell populations.Nature reviews. Immunology · 2026Article
- PD-L1-targeted OMV priming licenses myeloid co-stimulation and chemokine circuits to potentiate CAR-T therapy in advanced-stage solid tumors.Journal of nanobiotechnology · 2026Article
- Targeting tumor-specific T cells with LAG3-directed interleukin-2 prevents T-cell exhaustion and reinvigorates antitumor immunity.Signal transduction and targeted therapy · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Intratumoral Virus-Like Particles Containing a TLR9 Agonist Combined with Systemic αPD-1 Activate Tumor-Specific CD8+ T Cells.Cancer research communications · 2026Article
- Oxygen-carrying nanovaccine potentiates cancer immunotherapy for heterogeneous solid tumors.Materials today. Bio · 2026Article
555 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Commented on by
Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Programmed cell death-1 (PD-1)-targeted therapies enhance T cell responses and show efficacy in multiple cancers, but the role of costimulatory molecules in this T cell rescue remains elusive. Here, we demonstrate that the CD28/B7 costimulatory pathway is essential for effective PD-1 therapy during chronic viral infection. Conditional gene deletion showed a cell-intrinsic requirement of CD28 for CD8 T cell proliferation after PD-1 blockade. B7-costimulation was also necessary for effective PD-1 therapy in tumor-bearing mice. In addition, we found that CD8 T cells proliferating in blood after PD-1 therapy of lung cancer patients were predominantly CD28-positive. Taken together, these data demonstrate CD28-costimulation requirement for CD8 T cell rescue and suggest an important role for the CD28/B7 pathway in PD-1 therapy of cancer patients.
Indexed as
Identifiers
What Socratic 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 Socratic graph.