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Updated: Jun 5, 2026
08:49
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Ciclopirox reprograms effector responses and modulates Notch1 activation in activated human T cells
Aprajita Tripathi1, Debolina Dasgupta1, Mehak Ahuja1
1Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, USA.
Iscience
|June 4, 2026
Summary
Ciclopirox (CPX), an antifungal, impacts human T cell immunity. While enhancing early activation, CPX suppresses T cell expansion and effector functions by modulating Notch signaling and limiting T cell metabolism.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Ciclopirox (CPX) is an FDA-approved antifungal agent.
- Previous studies showed fosciclopirox inhibited cell proliferation and Notch signaling in cancer patients.
- The effects of CPX on human T cell function were previously undefined.
Purpose of the Study:
- To investigate the impact of CPX on primary human T cell activation.
- To define the effects of CPX on T cell effector responses.
- To elucidate the mechanisms by which CPX modulates T cell function.
Main Methods:
- Primary human T cells were treated with CPX.
- T cell activation markers, IL-2 production, and cell cycle progression were analyzed.
- IFN-γ production, cytotoxic granule expression, and T cell metabolism were assessed.
- Notch1 activation was monitored in CPX-treated T cells.
Main Results:
- CPX enhanced early T cell activation markers and IL-2 production.
- CPX suppressed T cell expansion, altered cell cycle progression, and reduced effector functions (IFN-γ, cytotoxic granules).
- CPX modulated Notch1 activation and limited T cell glycolysis, impacting T cell responses.
Conclusions:
- CPX acts as a modulator of human T cell immunity.
- CPX influences T cell activation, proliferation, and effector functions.
- These findings have implications for the therapeutic application of CPX in immunotherapy.
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