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December 8, 2025Journal for ImmunoTherapy of CancerOpen Access

TNF-α and IFN-γ differentially regulate AML cell susceptibility to CD70-antibody-mediated cytotoxicity

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Authors

KWKieron WhiteAMAndreas MaiserDRDaniel Richter

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Overview

Observations reveal enhanced cytotoxicity in AML via CD70-targeting antibody, suggesting resistance due to IFN-γ-induced immune escape mechanisms.

Key Points

  • Evaluate the role of CD70 in NK-cell-based immunotherapy for AML and the impact of cytokines on cytotoxicity.
  • Flow cytometry assessed CD70 expression in primary AML samples.
  • Antibody-dependent cellular cytotoxicity (ADCC) assays tested SEA-CD70's effectiveness on AML cells.
  • SCID mouse model evaluated in vivo efficacy of CD70-targeting immunotherapy.
  • Cytokine effects on CD70 expression were analyzed with conditioned media from activated T cells.
  • CD70 expression in primary AML cells ranged from 0.2% to 89.6%, with a median of 7.0%.
  • SEA-CD70 showed significant dose-dependent cytotoxicity against AML cells, correlating with CD70 levels.
  • TNF-α increased CD70 expression, enhancing cytotoxicity from 17.9% to 34.3%; IFN-γ reduced cytotoxicity to 9.2%.
  • Increased expression of NK inhibitory receptor ligands was linked to IFN-γ exposure, impacting ADCC effectiveness.

Cite This Study

White et al. (2025) studied this question.

synapsesocial.com/papers/693624d74fa91c937236d152https://doi.org/10.1136/jitc-2025-013024
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