Cancer Research

Mitochondrial Power Determines How Well Immune Cells Fight Cancer

Researchers at St. Jude Children's Research Hospital discovered that conventional type 1 dendritic cells (cDC1s) — immune cells critical for activating cancer-killing T cells — exist in two distinct mitochondrial states inside tumors. Cells with polarized, energized mitochondria were far better at presenting tumor antigens and activating CD8+ T cells than their counterparts with depolarized mitochondria. The protein OPA1, which controls mitochondrial fusion and cristae structure, emerged as the master regulator of this difference. Loss of OPA1 in dendritic cells accelerated tumor growth across multiple cancer models. Crucially, injecting cDC1s with boosted mitochondrial function into tumors significantly improved outcomes, especially when combined with immune checkpoint blockade. These findings point to mitochondrial metabolism as a new lever for cancer immunotherapy.