Research led by researchers in National Heart and Vascular Research Center (CNIC) has identified a mitochondrial “checkpoint” that allows dendritic cells to efficiently activate T lymphocytes against viruses and tumors. Dendritic cells are immune cells that detect threats and activate the body’s defenses, acting as “sentries” that tell T lymphocytes what to attack.
This research scientific immunologyshow that restoring the internal chemical imbalance caused by defects in mitochondrial function in dendritic cells restores the ability of immune cells to protect the body from infection. This discovery could open new avenues for improving cancer immunotherapy.
This study revealed that the ability of dendritic cells to activate T lymphocytes depends on an unexpected mechanism: the proper functioning of mitochondrial complex I, a key mitochondrial component. Mitochondrial complex I functions as a “metabolic switch” essential for the ability of dendritic cells to convert viral or tumor-derived material into effective immune activation signals and elicit strong T-cell responses.
The study, led by CNIC researcher David Sancho and Michelle Enamorado of the Icahn School of Medicine at Mount Sinai in New York, identified a new metabolic checkpoint that determines the effectiveness of this immune “coaching” process.
We discovered that mitochondrial complex I functions as a true metabolic switch. When dendritic cells do not function properly, they lose much of their ability to activate T lymphocytes to fight threats such as tumors and viruses. ”
Dr. David Sancho, CNIC Researcher
The co-lead authors of this study, Sofia C. Kuwili and Elena Priego (CNIC), emphasize that the function of mitochondrial complex I is important for dendritic cell-mediated activation of T lymphocytes.
Sofía C. Khouili explains, “When complex I function is impaired, dendritic cells struggle to present enough antigen to T lymphocytes, reducing both T cell activation and immune responses to viruses and tumors.”
Elena Priego adds, “The key lies in the increased NADH to NAD+ ratio resulting from complex I deficiency. Restoring the balance of this ratio by pharmacological means restores the ability of dendritic cells to activate T lymphocytes during viral infection or antitumor responses.”
According to Sancho and Enamorado, the mitochondrial activity of dendritic cells is altered in certain environments, such as the tumor microenvironment, which may limit their ability to activate T lymphocytes. “We identified mitochondrial complex I in dendritic cells as a critical checkpoint and demonstrated in experimental models that correcting internal chemical imbalances associated with its dysfunction can restore the immune response.”
The researchers concluded that these findings “suggest new strategies to enhance vaccines and cancer immunotherapy.”
sauce:
Carlos III National Center for Cardiovascular Research (FSP)
Reference magazines:
Coili, South Carolina, others. (2026). Mitochondrial complex I activity promotes antigen cross-presentation in dendritic cells. Science Immunology. DOI: 10.1126/scimmunol.aef0098. https://www.science.org/doi/10.1126/sciimmunol.aef0098
