Organelle-Selective Autophagy in Cancer Immunotherapy: Mitophagy and Nucleophagy-Related Nuclear Quality Control as Regulators of Tumor–Immune Interactions
- 1Department of Histology and Embryology, Faculty of Medicine, Istanbul Atlas University, Istanbul 34403, Türkiye
- 2Department of Obstetrics and Gynecology, Faculty of Medicine, Istanbul Atlas University, Istanbul 34403, Türkiye
Abstract
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.
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BibTeX
@article{bilir2026organelleselective,
title = {{Organelle-Selective Autophagy in Cancer Immunotherapy: Mitophagy and Nucleophagy-Related Nuclear Quality Control as Regulators of Tumor–Immune Interactions}},
author = {Ayhan Bilir and Berna Yıldırım and Mete Hakan Karalök},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198775},
url = {https://www.mdpi.com/1422-0067/27/19/8775},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Organelle-Selective Autophagy in Cancer Immunotherapy: Mitophagy and Nucleophagy-Related Nuclear Quality Control as Regulators of Tumor–Immune Interactions
AU - Ayhan Bilir
AU - Berna Yıldırım
AU - Mete Hakan Karalök
PY - 2026
DA - 2026/09/30
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198775
UR - https://www.mdpi.com/1422-0067/27/19/8775
AB - 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.
SN - 1422-0067
ER -