Related Experiment Video

Updated: Mar 25, 2026

Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
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Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells

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Pentose phosphate pathway fuels cGAS-STING signalling to boost function of intratumoral conventional dendritic cells

Ben Liu1,2, Zhonglei Geng2, Yujie Huang2

  • 1Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing Medical University, Nanjing, China.

Nature Communications
|March 24, 2026
PubMed

Insights

Tumor cells impair dendritic cell (DC) function by reducing the pentose phosphate pathway (PPP). Restoring PPP function in DCs enhances anti-tumor immunity and immunotherapy effectiveness.

Area of Science:

  • Immunology
  • Metabolic pathways
  • Cancer research

Background:

  • Tumors evade immune responses by impairing conventional dendritic cell (cDC) function.
  • The specific metabolic mechanisms by which tumors affect cDC function remain largely unknown.

Purpose of the Study:

  • To investigate the role of the pentose phosphate pathway (PPP) in cDC function within the tumor microenvironment.
  • To explore the potential of targeting PPP for enhancing anti-tumor immunity and cancer immunotherapy.

Main Methods:

  • Pharmacological and genetic inhibition/augmentation of the PPP in cDCs.
  • Assessment of cDC-mediated anti-tumor responses.
  • Analysis of immune checkpoint PD-L1 expression.
  • Investigation of purine metabolism and cGAS-STING signaling pathways.
  • Analysis of tumor tissues from breast cancer patients.

Main Results:

  • Reduced PPP activity in late-stage intratumoral cDCs compromises their anti-tumor function.
  • Inhibition of PPP attenuates cDC-mediated anti-tumor responses, while augmentation restores them.
  • PPP deficiency in cDCs increases PD-L1 expression.
  • Combining PPP potentiation with immune checkpoint blockade synergistically enhances immunotherapy.
  • PPP activation supports purine metabolism, ATP/GTP synthesis, 2'3'-cGAMP production, and cGAS-STING signaling.

Conclusions:

  • The PPP acts as a critical metabolic checkpoint for STING-mediated cDC anti-tumor immunity.
  • Targeting the PPP in cDCs represents a promising strategy for improving cancer immunotherapy outcomes.

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