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PU.1 regulation of type 1 dendritic cell function via NF-κB pathway in inhibition of non-small cell lung cancer

Tingting Wang1, Yishuo Li2, Qiongyu Duan3

  • 1Department of Gerontology, The First Hospital of China Medical University, Shenyang, 110001, China.

Journal of Pharmaceutical Analysis
|July 29, 2025
PubMed

Insights

Transcription factor PU.1 is underexpressed in non-small cell lung cancer (NSCLC), where it inhibits tumor growth by activating the nuclear factor kappaB (NF-κB) pathway in dendritic cells. This suggests PU.1 as a potential therapeutic target for NSCLC.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality.
  • Dendritic cells play a crucial role in anti-tumor immunity.
  • Understanding immune cell regulation within the tumor microenvironment is critical for developing effective therapies.

Purpose of the Study:

  • To investigate the regulatory role of transcription factor PU.1 in type 1 conventional dendritic cells (cDC1).
  • To explore the therapeutic potential of modulating the nuclear factor kappaB (NF-κB) signaling pathway in NSCLC.
  • To identify key regulators of cDC1 function in the context of NSCLC.

Main Methods:

  • Single-cell transcriptome sequencing was employed to analyze the immune cell landscape in NSCLC tissues.
  • Bioinformatics tools, including the CIBERSORT algorithm, were used for immune cell profiling.
  • In vivo models were utilized to validate the functional effects of PU.1.

Main Results:

  • Distinct NSCLC subtypes and cDC1 developmental trajectories were identified.
  • PU.1 was found to be underexpressed in NSCLC samples and critical for cDC1 function.
  • PU.1 induced the NF-κB pathway, inhibiting tumor proliferation and enhancing cDC1 activation.
  • In vivo studies confirmed PU.1's suppressive effect on NSCLC progression via cDC1 and the NF-κB pathway.

Conclusions:

  • PU.1 plays a significant role in regulating cDC1 function and anti-tumor immunity in NSCLC.
  • Modulation of the PU.1-NF-κB axis in cDC1s presents a promising therapeutic strategy for NSCLC.
  • Transcriptional regulators are important targets for cancer immunotherapy.
Keywords:
Immune infiltrationNF-κB signaling pathwayNon-small cell lung cancerPU.1Single-cell transcriptome sequencingcDC1

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