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Updated: Jul 1, 2025

Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy
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Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy

Published on: August 1, 2013

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PIKfyve controls dendritic cell function and tumor immunity

Jae Eun Choi1,2, Yuanyuan Qiao1,2,3, Ilona Kryczek4,5

  • 1Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

Biorxiv : the Preprint Server for Biology
|March 11, 2024
PubMed

Insights

Targeting PIKfyve enhances dendritic cell (DC) function, improving cancer immunotherapy. PIKfyve inhibition boosts DC-mediated T cell immunity and potentiates immune checkpoint blockade (ICB) efficacy, offering new strategies for cancer vaccines.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Cancer treatment increasingly utilizes immunotherapy and targeted therapies like protein kinase inhibitors.
  • Mechanisms linking cancer-targeting drugs to dendritic cell (DC) mobilization and immunotherapy effectiveness remain unclear.

Purpose of the Study:

  • To investigate the role of PIKFYVE gene expression in patient response to immune checkpoint blockade (ICB).
  • To explore the impact of PIKfyve inhibition on DC function and anti-tumor immunity.

Main Methods:

  • Analysis of PIKFYVE expression in relation to ICB response in cancer patients.
  • Genetic ablation and pharmacological inhibition of PIKfyve in dendritic cells.
  • Evaluation of tumor growth, T cell immunity, and ICB efficacy in preclinical mouse models.
  • Assessment of apilimod (PIKfyve inhibitor) in combination with vaccine adjuvants.

Main Results:

  • High PIKFYVE expression correlated with poorer complete response to ICB and reduced DC function.
  • PIKfyve ablation in DCs enhanced their function through the non-canonical NF-κB pathway.
  • PIKfyve inhibition (genetic or apilimod) suppressed tumor growth and improved DC-dependent T cell responses.
  • Apilimod treatment potentiated ICB efficacy and, with a vaccine adjuvant, reduced tumor progression in vivo.

Conclusions:

  • PIKfyve acts as a negative regulator of dendritic cell function.
  • PIKfyve inhibition demonstrates significant potential for enhancing cancer immunotherapy and vaccine strategies.
Keywords:
NF-κBPIKfyveantigen-specific T cellapilimodcancer vaccinedendritic cellimmune checkpoint blockadekinase inhibitortumor

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