Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity
Summary
Antitumor immunity requires conventional type 1 dendritic cells (cDC1s). How cDC1s maintain functional fitness in the tumor microenvironment remains unclear. In this study, we established that intratumoral cDC1s exhibited discrete mitochondrial states and that OPA1-mediated mitochondrial energy and redox metabolism dictated cDC1 antitumor responses. Mechanistically, OPA1 orchestrated antigen presentation and the CD8+ T cell priming function of cDC1s by promoting nuclear respiratory factor
Content
# Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity
*Published: 2026 Apr 2*
Antitumor immunity requires conventional type 1 dendritic cells (cDC1s). How
cDC1s maintain functional fitness in the tumor microenvironment remains unclear.
In this study, we established that intratumoral cDC1s exhibited discrete
mitochondrial states and that OPA1-mediated mitochondrial energy and redox
metabolism dictated cDC1 antitumor responses. Mechanistically, OPA1 orchestrated
antigen presentation and the CD8+ T cell priming function of cDC1s by promoting
nuclear respiratory factor 1 (NRF1) expression and electron transport chain
integrity, thereby supporting bioenergetics and NAD+/NADH balance. During tumor
progression, mitochondrial membrane potential and volume, as well as OPA1-NRF1
signaling, declined in intratumoral cDC1s. Furthermore, intratumoral
administration of cDC1s with polarized mitochondria showed immunotherapeutic
benefits in mice, particularly in combination with immune checkpoint blockade.
Collectively, our findings reveal mitochondrial metabolism and signaling as
putative targets to reinvigorate cDC1 function for cancer immunotherapy.
DOI: 10.1126/science.adv6582