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June 11, 2026Cancer Immunology ImmunotherapyOpen Access

Low-dose IL-2 therapy for immune-related adverse events via Tfh/Treg balance modulation: a prospective cohort and murine model study

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Authors

YWYifan WangZZZhening ZhangYLY L Li

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Overview

Prospective cohort analysis reveals LDIL-2 therapy improves Tfh/Treg balance in gastrointestinal cancer patients with irAEs, suggesting a novel treatment strategy.

Key Points

  • This study investigates the role of Tfh/Treg balance in immune-related adverse events and evaluates LDIL-2 therapy's efficacy in mitigating these effects.
  • 26 gastrointestinal cancer patients were evaluated before and after anti-PD-1/PD-L1 therapy through cellular and transcriptomic analyses.
  • Patients were categorized into the AE group (developed irAEs) and NAE group (did not develop irAEs).
  • Murine models, including MRL/MpJ-Fas lpr and tumor-bearing C57BL/6 J mice, were used to assess LDIL-2 treatment effects.
  • In AE patients, significant upregulation of Tfh-related genes (IL-21: p < 0.01; PDCD1: p < 0.05) was noted compared to Treg-related genes.
  • The Tfh/Treg ratio increased significantly in AE patients (p < 0.001), contrasting with NAE patients.
  • LDIL-2-treated mice showed a balanced Tfh/Treg ratio with fewer organ lesions and maintained antitumor efficacy during anti-PD-L1 therapy.

Cite This Study

Wang et al. (2026) studied this question.

synapsesocial.com/papers/6a2a515980c8f91e7f39da91https://doi.org/10.1007/s00262-026-04452-6
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