Pentose phosphate pathway fuels cGAS-STING signalling to boost function of intratumoral conventional dendritic cells - PubMed
5 hours ago
- #dendritic cells
- #metabolic pathways
- #cancer immunotherapy
- The pentose phosphate pathway (PPP) is crucial for the function of intratumoral conventional dendritic cells (cDCs).
- Reduction in PPP in late-stage intratumoral cDCs impairs their antitumor responses.
- Pharmacological and genetic inhibition of PPP attenuates cDC-mediated antitumor activity.
- Augmentation of PPP restores the antitumor capacity of late-stage intratumoral cDCs.
- PPP deficiency in cDCs increases PD-L1 expression, suggesting a link to immune checkpoint pathways.
- Combining PPP potentiation in cDCs with immune checkpoint blockade enhances immunotherapy efficacy.
- PPP activation fuels purine metabolism, increasing ATP and GTP levels necessary for 2'3'-cGAMP synthesis.
- Enhanced cGAS-STING signaling through PPP promotes STING-dependent cDC antitumor responses.
- PPP is associated with STING-dependent cDC activities in breast cancer tumor tissues.
- Targeting PPP in cDCs is proposed as a promising strategy for cancer immunotherapy.