ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Reshape the Fates of Treg and CD8+T Cells Through IL-2Rα by Synergizing Divergent Receptor-Biased IL-2 PEGylates.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed.
- A Tumor-Microenvironment-Responsive Chemically Masked IL‑2 Prodrug Potentiates PD‑1 Checkpoint Blockade and Elicits Robust Antitumor Efficacy.ACS central science · 2026Article
- Engineered iMSCs delivering wild-type IL-2 achieve dose-sparing tumor control via CD25-dependent CD8BMC medicine · 2026Article
- Regulatory T Cell-Related Gene Polymorphisms are Associated with Risk of Lung Cancer in Patients with COPD.International journal of chronic obstructive pulmonary disease · 2026Article
- Reshape the Fates of Treg and CD8+T Cells Through IL-2Rα by Synergizing Divergent Receptor-Biased IL-2 PEGylates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chemokines and their receptors in oral squamous cell carcinoma: mechanisms, clinical significance, and therapeutic implications.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors.
Funding
Abstract
Clinical trials of receptor-biased interleukin-2 (IL-2) variants in cancer therapy show limited efficacy. To investigate, we re-evaluated divergent receptor-biased IL-2 PEGylates (generated via site-specific PEGylation at residues D20 (not-β) and Y45 (not-α)), alone or in combination. Results showed the not-α variant (Y45) activates regulatory T cells (Tregs) via βγ chain binding, overriding CD8+ T cells and impairing efficacy. Conversely, the not-β IL-2 (D20) is inert alone but spatially blocks Y45's βγ engagement, suppressing Treg activation. D20 also modulates activated CD8+ T cells by preferentially binding the α chain, disrupting Y45-mediated βγ signaling to prevent exhaustion and terminal differentiation. Synergy between these PEGylates highlights the α chain as a regulatory switch reshaping Treg, CD8+ T cell, and endothelial cell fates. In syngeneic tumor models, combined therapy enhanced CD8+ T cell infiltration, suppressed tumor growth, and reduced vascular leak syndrome risk. These findings propose combinatorial IL-2 strategies targeting α chain regulation to optimize antitumor responses.
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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.