Organelle-Selective Autophagy in Cancer Immunotherapy: Mitophagy and Nucleophagy-Related Nuclear Quality Control as Regulators of Tumor–Immune Interactions

Organelle-selective autophagy is an important regulator of tumor adaptation, immune signaling, and therapeutic resistance. By directing specific intracellular cargos to lysosomal degradation, selective autophagy pathways determine whether organelle damage is eliminated or remains available to innate immune sensors. In cancer, this is particularly relevant because mitochondrial and nuclear damage can generate immunologically active signals that influence tumor–immune interactions. This review examines mitophagy and nucleophagy-related nuclear quality-control mechanisms as regulators of cancer immunity and immunotherapy response. Mitophagy can limit mitochondrial ROS and mtDNA release while supporting metabolic adaptation, whereas nuclear quality-control mechanisms, including lamin B1 degradation, micronuclear clearance, and cGAS-associated micronucleophagy, may regulate the persistence of nuclear-derived DNA signals. We propose the concept of “intracellular immune-signal editing” to describe how organelle-selective autophagy controls the persistence, accessibility, and duration of mitochondrial and nuclear danger signals. The immunological outcome is highly context- and compartment-dependent because autophagy may protect tumor cells while supporting mitochondrial fitness and effector function in immune cells. We also discuss therapeutic implications, biomarkers, and experimental strategies required to distinguish true organelle-selective autophagic flux from static marker changes.