ArticleThe Journal of clinical investigation2022
Selective delivery of low-affinity IL-2 to PD-1+ T cells rejuvenates antitumor immunity with reduced toxicity.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07593365 (Clinical Application of Vagus Nerve Stimulation Combined With Immunoregulatory T Cells in Alleviating Aromatase Inhibitor-Induced Pain), which is not on this map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Clinical Application of Vagus Nerve Stimulation Combined With Immunoregulatory T Cells in Alleviating Aromatase Inhibitor-Induced Pain
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effects of moxibustion therapies on immune function in cancer animal models: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Trial
- Endolysosomal routing combined with immune stimulation enhances anti-tumor efficacy of an HPV16 mRNA therapeutic vaccine.Materials today. Bio · 2026Article
- IL-2/CD25 acts within the tumor microenvironment to reprogram tumor-specific cytotoxic CD8Journal for immunotherapy of cancer · 2026Article
- De novo design of protease-activatable cytokine prodrugs.bioRxiv : the preprint server for biology · 2026Article
- Tumor-targeted IL-10 synergizes with IL-2 to enhance antitumor immunity while minimizing immune-related adverse events.Nature communications · 2026Article
- A Tumor-Microenvironment-Responsive Chemically Masked IL‑2 Prodrug Potentiates PD‑1 Checkpoint Blockade and Elicits Robust Antitumor Efficacy.ACS central science · 2026Article
- TIGIT-targeted IL-12 fusion protein engages NK and CD8Cell reports. Medicine · 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
- Targeting cytokine/chemokine signaling to convert immunologically cold tumors into hot: Emerging strategies in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Reprogramming the tumor microenvironment with antibody against membrane-proximal AXL to overcome immune checkpoint blockade resistance.Signal transduction and targeted therapy · 2026Article
- Article
- Reactivating exhausted tumor-infiltrating T cells by a bispecific DC-T cell engager in mice.Nature communications · 2026Article
- Dual PD-1/IL-2Rα targeting restores CD8Cell reports. Medicine · 2026Article
- Rewiring tumor cytokine networks to enhance immune checkpoint blockade: mechanisms, engineering, and clinical translation.Journal of experimental & clinical cancer research : CR · 2026Review
- Circulating cytokines as potential dynamic biomarkers of PD-1 blockade response and prognosis in non-small cell lung cancer.Frontiers in immunology · 2026Review
- Non-α-biased IL-2 enhances both intratumoral and subcutaneous CpG/α-OX40 therapy, unleashing systemic antitumor immunity in mice.Journal for immunotherapy of cancer · 2025Article
- Review
- Protein engineering to overcome limitations of key cytokines in cancer immunotherapy: current approaches and future perspectives.Immuno-oncology technology · 2025Review
- αTIGIT-IL2 achieves tumor regression by promoting tumor-infiltrating regulatory T cell fragility in mouse models.Nature communications · 2025Article
9 more citing papers are in PubMed but not listed here.
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8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
PD-1 signaling on T cells is the major pathway that limits T cell immunity, but the efficacy of anti-PD-1 therapy has been limited to a small proportion of patients with advanced cancers. We fortuitously observed that anti-PD-1 therapy depends on IL-2 signaling, which raises the possibility that a lack of IL-2 limits anti-PD-1-induced effector T cell expansion. To selectively deliver IL-2 to PD-1+CD8+ tumor-infiltrating lymphocytes (TILs), we engineered a low-affinity IL-2 paired with anti-PD-1 (PD-1-laIL-2), which reduced affinity to peripheral Treg cells but enhanced avidity to PD-1+CD8+ TILs. PD-1-laIL-2 exerted better tumor control and lower toxicity than single or mixed treatments. Mechanistically, PD-1-laIL-2 could effectively expand dysfunctional and tumor-specific CD8+ T cells. Furthermore, we discovered that presumably dysfunctional PD-1+TIM3+ TILs are the dominant tumor-specific T cells responding to PD-1-laIL-2. Collectively, these results highlight that PD-1-laIL-2 can target and reactivate tumor-specific TILs for tumor regression as a unique strategy with stronger efficacy and lower toxicity.
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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.