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December 8, 2025Blood

IL‑10 limits CLL progression by reprogramming T cell exhaustion and myeloid suppression

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Authors

AFAlessia FloerchingerHBHannah Briesch

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Overview

Preclinical findings show IL-10 enhances cytotoxic T cell function in chronic lymphocytic leukemia, highlighting potential synergy with ibrutinib.

Key Points

  • This research aims to investigate the role of IL-10 in modulating T cell exhaustion and its potential as a therapeutic target in chronic lymphocytic leukemia.
  • Utilized the Eµ-TCL1 adoptive transfer mouse model of CLL.
  • Developed a stabilized IL-10 fusion protein (IL-10-Fc) for therapeutic trials.
  • Conducted in vitro assays on TCR-transgenic murine CD8⁺ T cells under antigen-specific stimulation.
  • Performed spectral flow cytometry and single-cell RNA-sequencing to analyze immune compartment alterations.
  • Explored combination therapy of IL-10-Fc with the BTK inhibitor ibrutinib.
  • IL-10 treatment slowed CLL progression and reduced exhausted effector T cells.
  • Therapy preserved TPEX populations and promoted a polyfunctional T cell phenotype.
  • IL-10-Fc reduced PD-L1⁺ patrolling monocytes linked to immune suppression.
  • Combination treatment with IL-10-Fc and ibrutinib achieved improved disease control.

Cite This Study

Floerchinger et al. (2025) studied this question.

synapsesocial.com/papers/69362f5d4fa91c937236dc65https://doi.org/10.1182/blood-2025-242
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Leukemic cell-secreted interleukin-9 suppresses cytotoxic T cell-mediated killing in chronic lymphocytic leukemia2024 · 6 citations
  2. 2Functional differences between CLL‐ and ALL‐derived CAR T cells in a 3D tumor microenvironment highlight CXCR4 and IL‐10 as potential modulatory targets2025 · 2 citations
  3. 3T-cell dysfunction in CLL is mediated through expression of SIGLEC-10 ligands CD24 and CD52 on CLL cells2024 · 8 citations
  4. 4CD4+ T cells sustain aggressive chronic lymphocytic leukemia in Eμ-TCL1 mice through a CD40L-independent mechanism2021 · 18 citations
  5. 5Integrative multi-omics identifies regulatory and exhausted T cell types and novel immunotherapy targets in CLL lymph nodes2024