ArticleThe Journal of experimental medicine2025
PD-1 regulates tumor-infiltrating CD8+ T cells in both a cell-intrinsic and a cell-extrinsic fashion.
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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
6 citing papers in PubMed.
- PD-1 regulates CD4Nature communications · 2026Article
- PD-1 regulates latent effector differentiation of thymic cytotoxic CD8Nature communications · 2026Article
- Mitophagy-driven multidimensional regulation of tumor immune evasion and context-dependent therapeutic strategies.Journal of translational medicine · 2026Review
- The Proximity of PD-1Cancers · 2026Article
- Single-Cell Sequencing Unravels Pancreatic Cancer: Novel Technologies Reveal Novel Aspects of Cellular Heterogeneity and Inform Therapeutic Strategies.Biomedicines · 2025Review
- Dual-faced circRNAs: orchestrating immunosuppression and activation in the lung cancer microenvironment.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Although PD-1 inhibitors are FDA-approved for over 25 different cancers, the mechanisms contributing to response remain incompletely understood. To investigate how PD-1-deleted CD8+ T cells influence PD-1-expressing CD8+ T cells in the same tumor microenvironment, we developed an inducible PD-1 knockout (KO) model in which PD-1 is deleted on ∼50% of cells. PD-1 deletion beginning at day 7 after implantation of MC38 tumor cells led to robust tumor control. Remarkably, PD-1-expressing CD8+ T cells in the tumor had increased functionality similar to PD-1 KO CD8+ T cells. Using single-cell RNA-seq and TCR-seq, we found that the major transcriptional changes following PD-1 deletion were shared by PD-1 KO and PD-1-expressing CD8+ T cells, although PD-1 KO clones preferentially expanded. These data suggest PD-1 inhibitors not only exert cell-intrinsic effects but also may promote increased T cell function through non-cell-autonomous mechanisms, which has important implications for design of PD-1-based cancer immunotherapies.
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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.