{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:58:01Z","timestamp":1790780281808,"version":"4.1.0"},"reference-count":114,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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\u2013immune 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 \u201cintracellular immune-signal editing\u201d 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.<\/jats:p>","DOI":"10.3390\/ijms27198775","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:19:37Z","timestamp":1790777977000},"page":"8775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Organelle-Selective Autophagy in Cancer Immunotherapy: Mitophagy and Nucleophagy-Related Nuclear Quality Control as Regulators of Tumor\u2013Immune Interactions"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9399-5927","authenticated-orcid":false,"given":"Ayhan","family":"Bilir","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Istanbul Atlas University, Istanbul 34403, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4479-2586","authenticated-orcid":false,"given":"Berna","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Istanbul Atlas University, Istanbul 34403, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mete Hakan","family":"Karal\u00f6k","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Istanbul Atlas University, Istanbul 34403, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, adaptive, and acquired resistance to cancer immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41577-019-0218-4","article-title":"Tumour-intrinsic resistance to immune checkpoint blockade","volume":"20","author":"Kalbasi","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12943-024-01934-y","article-title":"Selective autophagy in cancer: Mechanisms, therapeutic implications, and future perspectives","volume":"23","author":"Liu","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41556-018-0037-z","article-title":"Cargo recognition and degradation by selective autophagy","volume":"20","author":"Gatica","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.molcel.2019.09.005","article-title":"A diversity of selective autophagy receptors determines the specificity of the autophagy pathway","volume":"76","author":"Kirkin","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1172\/JCI73941","article-title":"The role for autophagy in cancer","volume":"125","author":"White","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1158\/2159-8290.CD-19-0292","article-title":"Targeting autophagy in cancer: Recent advances and future directions","volume":"9","author":"Amaravadi","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41392-023-01503-7","article-title":"The mitophagy pathway and its implications in human diseases","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e104705","DOI":"10.15252\/embj.2020104705","article-title":"Molecular mechanisms and physiological functions of mitophagy","volume":"40","author":"Onishi","year":"2021","journal-title":"EMBO J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/s41556-018-0176-2","article-title":"Mechanisms of mitophagy in cellular homeostasis, physiology and pathology","volume":"20","author":"Palikaras","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nri.2017.21","article-title":"Mitochondrial DNA in innate immune responses and inflammatory pathology","volume":"17","author":"West","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e49799","DOI":"10.15252\/embr.201949799","article-title":"Mitochondrial DNA in inflammation and immunity","volume":"21","author":"Riley","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41576-019-0151-1","article-title":"DNA sensing by the cGAS\u2013STING pathway in health and disease","volume":"20","author":"Motwani","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature15548","article-title":"Autophagy mediates degradation of nuclear lamina","volume":"527","author":"Dou","year":"2015","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.devcel.2015.11.016","article-title":"Autophagy devours the nuclear lamina to thwart oncogenic stress","volume":"35","author":"Leidal","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nature23449","article-title":"CGAS surveillance of micronuclei links genome instability to innate immunity","volume":"548","author":"Mackenzie","year":"2017","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nature23470","article-title":"Mitotic progression following DNA damage enables pattern recognition within micronuclei","volume":"548","author":"Harding","year":"2017","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3976","DOI":"10.1080\/15548627.2021.1899440","article-title":"CGAS is a micronucleophagy receptor for the clearance of micronuclei","volume":"17","author":"Zhao","year":"2021","journal-title":"Autophagy"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jalouli, M., Harrath, A.H., Al-Zharani, M., and Rahman, M.A. (2026). Autophagy Modulation in Cancer Immunotherapy, Emerging Molecular Targets and Drug Selection Strategies. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27052183"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1080\/15548627.2025.2455158","article-title":"Mammalian nucleophagy: Process and function","volume":"21","author":"Ji","year":"2025","journal-title":"Autophagy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s12943-026-02615-8","article-title":"The multifaceted functions of selective autophagy in cancer: Molecular basis, consequences, and clinical prospects","volume":"25","author":"Jiang","year":"2026","journal-title":"Mol. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e202002085","DOI":"10.1083\/jcb.202002085","article-title":"Autophagosome biogenesis: From membrane growth to closure","volume":"219","author":"Melia","year":"2020","journal-title":"J. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1056\/NEJMra2022774","article-title":"Autophagy in human diseases","volume":"383","author":"Mizushima","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy","volume":"17","author":"Klionsky","year":"2021","journal-title":"Autophagy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/jb\/mvag048","article-title":"BNIP3\/NIX-dependent mitophagy: Molecular mechanisms and physiological roles","volume":"180","author":"Ginevskaia","year":"2026","journal-title":"J. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"jcs222836","DOI":"10.1242\/jcs.222836","article-title":"P62\/SQSTM1\u2014Steering the cell through health and disease","volume":"131","author":"Komatsu","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nature14893","article-title":"The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy","volume":"524","author":"Lazarou","year":"2015","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nature13392","article-title":"Ubiquitin is phosphorylated by PINK1 to activate Parkin","volume":"510","author":"Koyano","year":"2014","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.molcel.2015.08.016","article-title":"The PINK1\u2013PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN\/NDP52 recruitment and TBK1 activation to promote mitophagy","volume":"60","author":"Heo","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jmb.2019.06.032","article-title":"Outstanding questions in mitophagy: What we do and do not know","volume":"432","author":"Ganley","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jare.2024.05.009","article-title":"Targeting selective autophagy and beyond: From underlying mechanisms to potential therapies","volume":"65","author":"Ma","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1080\/15548627.2015.1127465","article-title":"Mammalian autophagy degrades nuclear constituents in response to tumorigenic stress","volume":"12","author":"Dou","year":"2016","journal-title":"Autophagy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.15252\/embr.201540759","article-title":"Mitophagy defects arising from BNip3 loss promote mammary tumor progression to metastasis","volume":"16","author":"Chourasia","year":"2015","journal-title":"EMBO Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41419-021-04469-y","article-title":"BNIP3L\/NIX-mediated mitophagy: Molecular mechanisms and implications for human disease","volume":"13","author":"Li","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1080\/15548627.2016.1151580","article-title":"Mitophagy receptor FUNDC1 regulates mitochondrial dynamics and mitophagy","volume":"12","author":"Chen","year":"2016","journal-title":"Autophagy"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Konstantinidis, G., and Tavernarakis, N. (2022). Autophagy of the nucleus in health and disease. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.814955"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.cell.2013.06.007","article-title":"Catastrophic nuclear envelope collapse in cancer cell micronuclei","volume":"154","author":"Hatch","year":"2013","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00018-024-05380-3","article-title":"R-loops and impaired autophagy trigger cGAS-dependent inflammation via micronuclei formation in Senataxin-deficient cells","volume":"81","author":"Zannini","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/s41556-026-01961-5","article-title":"Nucleophagy removes cytotoxic trapped PARP1","volume":"28","author":"Hoslett","year":"2026","journal-title":"Nat. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1083\/jcb.201402104","article-title":"PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity","volume":"205","author":"Kane","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Huang, N., Liu, Z., Lei, H., and Liu, X. (2026). The roles of the mtDNA\u2013cGAS\u2013STING axis in tumor immunity: From immune activation to immune evasion. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1739559"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yan, X., Ding, H., Ren, M., and Zang, L. (2025). Mitophagy in the mechanisms of treatment resistance in solid tumors. Oncol. Rev., 19.","DOI":"10.3389\/or.2025.1607983"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101385","DOI":"10.1016\/j.mam.2025.101385","article-title":"Mitophagy: A key regulator of radiotherapy resistance in the tumor immune microenvironment","volume":"105","author":"Xia","year":"2025","journal-title":"Mol. Asp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/s41577-021-00524-z","article-title":"The cGAS\u2013STING pathway as a therapeutic target in inflammatory diseases","volume":"21","author":"Decout","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/ni.1980","article-title":"Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome","volume":"12","author":"Nakahira","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41422-022-00766-z","article-title":"Targeting ATAD3A\u2013PINK1\u2013mitophagy axis overcomes chemoimmunotherapy resistance by redirecting PD-L1 to mitochondria","volume":"33","author":"Xie","year":"2023","journal-title":"Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41422-023-00777-4","article-title":"Mitochondrial PD-L1 modulates cancer immunotherapy","volume":"33","author":"Dai","year":"2023","journal-title":"Cell Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.cell.2018.08.027","article-title":"The multifaceted role of chromosomal instability in cancer and its microenvironment","volume":"174","author":"Bakhoum","year":"2018","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"eaba0712","DOI":"10.1126\/science.aba0712","article-title":"Mechanisms generating cancer genome complexity from a single cell division error","volume":"368","author":"Umbreit","year":"2020","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1091\/mbc.e02-08-0483","article-title":"Piecemeal microautophagy of nucleus in Saccharomyces cerevisiae","volume":"14","author":"Roberts","year":"2003","journal-title":"Mol. Biol. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"213","DOI":"10.4161\/nucl.11738","article-title":"The intricacy of nuclear membrane dynamics during nucleophagy","volume":"1","author":"Mijaljica","year":"2010","journal-title":"Nucleus"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1101\/gad.179515.111","article-title":"The role of nuclear lamin B1 in cell proliferation and senescence","volume":"25","author":"Shimi","year":"2011","journal-title":"Genes Dev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.tcb.2017.08.004","article-title":"Nuclear lamins: Thin filaments with major functions","volume":"28","author":"Gruenbaum","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.aad7297","article-title":"Nuclear envelope rupture and repair during cancer cell migration","volume":"352","author":"Denais","year":"2016","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"15408","DOI":"10.1073\/pnas.1512832112","article-title":"STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity","volume":"112","author":"Demaria","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nature25432","article-title":"Chromosomal instability drives metastasis through a cytosolic DNA response","volume":"553","author":"Bakhoum","year":"2018","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"15618","DOI":"10.1038\/ncomms15618","article-title":"DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity","volume":"8","author":"Alard","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1042\/BST20220838","article-title":"CGAS\u2013STING signalling in cancer: Striking a balance with chromosomal instability","volume":"51","author":"Beernaert","year":"2023","journal-title":"Biochem. Soc. Trans."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s41571-020-0413-z","article-title":"Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors","volume":"17","author":"Galluzzi","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.biocel.2015.01.026","article-title":"The complex crosstalk between mitochondria and the nucleus: What goes in between?","volume":"63","author":"Cagin","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1093\/carcin\/bgaa114","article-title":"DNA damage and mitochondria in cancer and aging","volume":"41","author":"Patel","year":"2020","journal-title":"Carcinogenesis"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.cell.2012.02.035","article-title":"Mitochondria: In sickness and in health","volume":"148","author":"Nunnari","year":"2012","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nrc3380","article-title":"Immunogenic cell death and DAMPs in cancer therapy","volume":"12","author":"Krysko","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nri.2016.107","article-title":"Immunogenic cell death in cancer and infectious disease","volume":"17","author":"Galluzzi","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41586-020-2229-5","article-title":"Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I","volume":"581","author":"Yamamoto","year":"2020","journal-title":"Nature"},{"key":"ref_66","first-page":"e201909033","article-title":"Autophagy and cancer: Modulation of cell death pathways and cancer cell adaptations","volume":"219","author":"Towers","year":"2020","journal-title":"J. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1002\/1878-0261.12774","article-title":"Autophagy, the innate immune response and cancer","volume":"14","author":"Gerada","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12943-020-1138-4","article-title":"Autophagy and autophagy-related proteins in cancer","volume":"19","author":"Li","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/imm.70146","article-title":"Reprogramming autophagy to strengthen antitumour immunity: Advances in immunotherapeutic strategies","volume":"179","author":"Jyothi","year":"2026","journal-title":"Immunology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41568-021-00344-2","article-title":"Autophagy in tumour immunity and therapy","volume":"21","author":"Xia","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1101\/gad.325514.119","article-title":"Role of tumor and host autophagy in cancer metabolism","volume":"33","author":"White","year":"2019","journal-title":"Genes Dev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.cmet.2017.04.004","article-title":"Autophagy and tumor metabolism","volume":"25","author":"Kimmelman","year":"2017","journal-title":"Cell Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/ni.3025","article-title":"Autophagy is essential for effector CD8+ T cell survival and memory formation","volume":"15","author":"Xu","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.4049\/jimmunol.0801143","article-title":"Autophagy is essential for mitochondrial clearance in mature T lymphocytes","volume":"182","author":"Pua","year":"2009","journal-title":"J. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"7349","DOI":"10.4049\/jimmunol.1000576","article-title":"Macroautophagy regulates energy metabolism during effector T cell activation","volume":"185","author":"Hubbard","year":"2010","journal-title":"J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41590-020-00834-9","article-title":"Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion","volume":"22","author":"Scharping","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/imr.12422","article-title":"Autophagy proteins in antigen processing for presentation on MHC molecules","volume":"272","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.celrep.2016.04.002","article-title":"Macroautophagy proteins control MHC class I levels on dendritic cells and shape anti-viral CD8+ T cell responses","volume":"15","author":"Loi","year":"2016","journal-title":"Cell Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1080\/15548627.2017.1297907","article-title":"The autophagy machinery restrains iNKT cell activation through CD1D1 internalization","volume":"13","author":"Keller","year":"2017","journal-title":"Autophagy"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.immuni.2015.07.012","article-title":"BNIP3- and BNIP3L-mediated mitophagy promotes the generation of natural killer cell memory","volume":"43","author":"Johnson","year":"2015","journal-title":"Immunity"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/imr.13316","article-title":"Metabolic adaptations determine whether natural killer cells fail or thrive within the tumor microenvironment","volume":"323","author":"Moinuddin","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e141115","DOI":"10.1172\/jci.insight.141115","article-title":"Autophagic adaptation to oxidative stress alters peritoneal residential macrophage survival and ovarian cancer metastasis","volume":"5","author":"Xia","year":"2020","journal-title":"JCI Insight"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/cmi.2018.2","article-title":"Autophagy in dendritic cells","volume":"15","author":"Ghislat","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nri3532","article-title":"Autophagy in infection, inflammation and immunity","volume":"13","author":"Deretic","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Biasizzo, M., and Kopitar-Jerala, N. (2020). Interplay between NLRP3 inflammasome and autophagy. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.591803"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.cell.2015.12.057","article-title":"NF-\u03baB restricts inflammasome activation via elimination of damaged mitochondria","volume":"164","author":"Zhong","year":"2016","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Thorburn, A. (2014). Autophagy and its effects: Making sense of double-edged swords. PLoS Biol., 12.","DOI":"10.1371\/journal.pbio.1001967"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e37376","DOI":"10.1016\/j.heliyon.2024.e37376","article-title":"Targeting autophagy can synergize the efficacy of immune checkpoint inhibitors against therapeutic resistance: New promising strategy to reinvigorate cancer therapy","volume":"10","author":"Hashemi","year":"2024","journal-title":"Heliyon"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e012864","DOI":"10.1136\/jitc-2025-012864","article-title":"Clinical and translational results from a phase 1 trial of gemcitabine\/nab-paclitaxel with nivolumab\/ipilimumab or hydroxychloroquine\/ipilimumab in untreated metastatic pancreatic adenocarcinoma","volume":"14","author":"Cabanski","year":"2026","journal-title":"J. Immunother. Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.trecan.2024.11.001","article-title":"Cancer immunotherapeutic challenges from autophagy\u2013immune checkpoint reciprocal regulation","volume":"11","author":"Zhang","year":"2025","journal-title":"Trends Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Wang, B., Yu, W., Jiang, H., Meng, X., Tang, D., and Liu, D. (2024). Clinical applications of STING agonists in cancer immunotherapy: Current progress and future prospects. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1485546"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1158\/1078-0432.CCR-22-2235","article-title":"Combination of the STING Agonist MIW815 (ADU-S100) and PD-1 Inhibitor Spartalizumab in Advanced\/Metastatic Solid Tumors or Lymphomas: An Open-Label, Multicenter, Phase Ib Study","volume":"29","author":"Sweis","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3400","DOI":"10.1158\/1078-0432.CCR-24-3630","article-title":"Phase I and II Clinical Studies of the STING Agonist Ulevostinag with and without Pembrolizumab in Participants with Advanced or Metastatic Solid Tumors or Lymphomas","volume":"31","author":"Harrington","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Alabi, F., Imodoye, S.O., Adedokun, K.A., Eltokhy, M.A., Curcic, M., Okoyeocha, E., Thapa, I., Tiwari, S., Ogundele, A.V., and Ayo, T.E. (2026). The cGAS\u2013STING pathway in cancer immunotherapy: Prognostic value and therapeutic potential. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1760947"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/j.tibs.2020.07.006","article-title":"Autophagy assays for biological discovery and therapeutic development","volume":"45","author":"Mizushima","year":"2020","journal-title":"Trends Biochem. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ceb.2009.11.015","article-title":"Hypoxia-induced autophagy: Cell death or cell survival?","volume":"22","author":"Mazure","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1126\/science.aad7611","article-title":"ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death","volume":"352","author":"Raab","year":"2016","journal-title":"Science"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neo.2014.12.004","article-title":"Spherical cancer models in tumor biology","volume":"17","author":"Weiswald","year":"2015","journal-title":"Neoplasia"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"19103","DOI":"10.1038\/srep19103","article-title":"3D tumor spheroid models for in vitro therapeutic screening: A systematic approach to enhance the biological relevance of data obtained","volume":"6","author":"Zanoni","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/bit.26845","article-title":"3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs","volume":"116","author":"Nunes","year":"2019","journal-title":"Biotechnol. Bioeng."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.tibtech.2012.12.003","article-title":"Spheroid culture as a tool for creating 3D complex tissues","volume":"31","author":"Fennema","year":"2013","journal-title":"Trends Biotechnol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/s41580-020-0259-3","article-title":"Human organoids: Model systems for human biology and medicine","volume":"21","author":"Kim","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1038\/s12276-024-01272-5","article-title":"Patient-derived tumor organoids: A new avenue for preclinical research and precision medicine in oncology","volume":"56","author":"Thorel","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.it.2020.06.010","article-title":"Organoid models of tumor immunology","volume":"41","author":"Yuki","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1158\/2159-8290.CD-17-0833","article-title":"Ex vivo profiling of PD-1 blockade using organotypic tumor spheroids","volume":"8","author":"Jenkins","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41577-023-00896-4","article-title":"Harnessing 3D in vitro systems to model immune responses to solid tumours: A step towards improving and creating personalized immunotherapies","volume":"24","author":"Zhou","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.chembiol.2011.05.013","article-title":"A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery","volume":"18","author":"Katayama","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1083\/jcb.201603039","article-title":"Mito-QC illuminates mitophagy and mitochondrial architecture in vivo","volume":"214","author":"McWilliams","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1038\/nprot.2017.060","article-title":"A fluorescence-based imaging method to measure in vitro and in vivo mitophagy using mt-Keima","volume":"12","author":"Sun","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"37652","DOI":"10.1038\/s41598-025-21569-3","article-title":"Ultrastructural evaluation of lithium-induced autophagic and mitochondrial stress in 3D endometrial and neuroblastoma spheroids","volume":"15","author":"Bilir","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Y\u0131ld\u0131r\u0131m, B., Biltekin, B., Karal\u00f6k, M.H., and Bilir, A. (2026). Mitochondrial Injury Accompanied by Intermediate Filament Remodeling Following Lithium Chloride Exposure in 3D Endometrial Cancer Spheroids. Biomedicines, 14.","DOI":"10.20944\/preprints202602.1013.v1"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Bilir, A., Y\u0131ld\u0131r\u0131m, B., Karal\u00f6k, M.H., and Kulak, K. (2026). Lithium Chloride-Induced Nuclear Envelope Remodeling in 3D Endometrial Cancer Spheroids. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27146352"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s12943-025-02277-y","article-title":"Autophagy in tumor immune escape and immunotherapy","volume":"24","author":"Wang","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1007\/s12032-025-03081-w","article-title":"Targeting autophagy to enhance cancer immunotherapy: Emerging mechanisms and strategies","volume":"42","author":"Almutairi","year":"2025","journal-title":"Med. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8775\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:20:21Z","timestamp":1790778021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":114,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198775"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198775","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]}}}