Dendritic cell vaccines based on immunogenic cell death elicit danger signals and T cell–driven rejection of high-grade glioma
Abstract
Combining an immunogenic cell death inducer with dendritic cell immunotherapy treats high-grade glioma in a preclinical model.
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ICD can be initiated by viral infection, some FDA-approved chemotherapeutics (e.g., anthracyclines, bortezomib), specific forms of radiation therapy, and hypericin-based photodynamic therapy.
“ICD can be initiated by a relatively restricted set of stimuli, including viral infection, some FDA-approved chemotherapeutics (e.g., anthracyclines, bortezomib), specific forms of radiation therapy, and hypericin-based photodynamic therapy [854–861].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [859]
Cytotoxic therapies such as radiation and chemotherapy can increase the neoantigen load of tumours that have a low baseline neoantigen load, which is a barrier to effective immunotherapy.
“cytotoxic therapies (radiation and chemotherapy) can be used to increase the neoantigen load of tumours that have a low baseline neoantigen load, which is a barrier to effective immunotherapy121.”
From Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges (2018) · cites this paper as [121]
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Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges
Fukumura, D., Kloepper, J., Amoozgar, Z., Duda, D. G., & Jain, R. K. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2018.29 · Cited by 2,027 · see citing works
The Microenvironmental Landscape of Brain Tumors
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Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors
Galluzzi, L., Humeau, J., Buqué, A., Zitvogel, L., & Kroemer, G. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0413-z · Cited by 1,349 · see citing works
Consensus guidelines for the definition, detection and interpretation of immunogenic cell death
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Self-citationDendritic cell-based immunotherapy
Sabado, R. L., Balan, S., & Bhardwaj, N. (2016) · Cell Research · doi:10.1038/cr.2016.157 · Cited by 926 · see citing works
Immunogenic cell death in cancer therapy: Present and emerging inducers
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Defining the role of the tumor vasculature in antitumor immunity and immunotherapy
Schaaf, M. B., Garg, A. D., & Agostinis, P. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0061-0 · Cited by 629 · see citing works
Self-citationTargeting immunogenic cancer cell death by photodynamic therapy: past, present and future
Alzeibak, R., Mishchenko, T. A., Shilyagina, N. Y., Владимировна, Б. И., Vedunova, M. V., & Krysko, D. V. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001926 · Cited by 579 · see citing works
Targeting immunogenic cell stress and death for cancer therapy
Galluzzi, L., Guilbaud, E., Schmidt, D. R., Kroemer, G., & Marincola, F. M. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-00920-9 · Cited by 595 · see citing works
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Cell death in photodynamic therapy: From oxidative stress to anti-tumor immunity
Donohoe, C. L., Senge, M. O., Arnaut, L. G., & Gomes-da-Silva, L. C. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.07.003 · Cited by 444 · see citing works
Cell death and immunity in cancer: From danger signals to mimicry of pathogen defense responses
Garg, A. D., & Agostinis, P. (2017) · Immunological Reviews · doi:10.1111/imr.12574 · Cited by 448 · see citing works
Self-citationEngineered exosomes as an in situ DC-primed vaccine to boost antitumor immunity in breast cancer
Huang, L., Rong, Y., Tang, X., Yi, K., Qi, P., Hou, J., Liu, W., He, Y. Z., Gao, X., Yuan, C., et al. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01515-x · Cited by 413 · see citing works
Gunaydin, G., Gedik, M. E., & Ayan, S. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.686303 · Cited by 402 · see citing works
A melanin-mediated cancer immunotherapy patch
Ye, Y., Wang, C., Zhang, X., Hu, Q., Zhang, Y., Liu, Q., Wen, D., Milligan, J. J., Bellotti, A., Huang, L., et al. (2017) · Science Immunology · doi:10.1126/sciimmunol.aan5692 · Cited by 382 · see citing works
Pathological Mechanism of Photodynamic Therapy and Photothermal Therapy Based on Nanoparticles
Hou, Y., Yang, X., Liu, R., Zhao, D., Guo, C., Zhu, A., Wen, M., Liu, Z., Qu, G., & Meng, H. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s269321 · Cited by 351 · see citing works
Integrating next-generation dendritic cell vaccines into the current cancer immunotherapy landscape
Garg, A. D., Coulie, P. G., Van den Eynde, B. J., & Agostinis, P. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.05.006 · Cited by 340 · see citing works
Self-citationSong, W. L., Kuang, J., Li, C., Zhang, M., Zheng, D., Zeng, X., Liu, C., & Zhang, X. (2018) · ACS Nano · doi:10.1021/acsnano.7b09112 · Cited by 313 · see citing works
Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics
Garg, A. D., More, S., Rufo, N., Meçe, O., Sassano, M. L., Agostinis, P., Zitvogel, L., Kroemer, G., & Galluzzi, L. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1386829 · Cited by 277 · see citing works
Self-citationAntitumour dendritic cell vaccination in a priming and boosting approach
Harari, A., Graciotti, M., Bassani‐Sternberg, M., & Kandalaft, L. E. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0074-8 · Cited by 271 · see citing works
Antigen cross-presentation and T-cell cross-priming in cancer immunology and immunotherapy
Sánchez-Paulete, A. R., Teijeira, Á., Cueto, F. J., Garasa, S., Perez‐Gracia, J. L., Sánchez-Arráez, Á., Sancho, D., & Melero, I. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx237 · Cited by 267 · see citing works
A Polymer Multicellular Nanoengager for Synergistic NIR‐II Photothermal Immunotherapy
Xu, C., Jiang, Y., Han, Y., Pu, K., & Zhang, R. (2021) · Advanced Materials · doi:10.1002/adma.202008061 · Cited by 235 · see citing works
β-Catenin induces transcriptional expression of PD-L1 to promote glioblastoma immune evasion
Du, L., Lee, J., Jiang, H., Wang, C., Wang, S., Zheng, Z., Shao, F., Xu, D., Xia, Y., Li, J., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191115 · Cited by 230 · see citing works
Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology
Vanmeerbeek, I., Sprooten, J., Ruysscher, D. D., Tejpar, S., Vandenberghe, P., Fucikova, J. P., Špíšek, R., Zitvogel, L., Kroemer, G., Galluzzi, L., et al. (2020) · OncoImmunology · doi:10.1080/2162402x.2019.1703449 · Cited by 226 · see citing works
Self-citationThe Unfolded Protein Response in Immunogenic Cell Death and Cancer Immunotherapy
Rufo, N., Garg, A. D., & Agostinis, P. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.07.002 · Cited by 211 · see citing works
Self-citationOrigin and Consequences of Necroinflammation
Sarhan, M., Land, W. G., Tonnus, W., Hugo, C., & Linkermann, A. (2018) · Physiological Reviews · doi:10.1152/physrev.00041.2016 · Cited by 210 · see citing works
Immunotherapy for glioblastoma: the promise of combination strategies
Bausart, M., Véronique Préat, A., & Malfanti, A. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02251-2 · Cited by 201 · see citing works
Immunogenic Cell Death and Immunotherapy of Multiple Myeloma
del Valle, A. S., Anel, A., Naval, J., & Marzo, I. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00050 · Cited by 196 · see citing works
Photodynamic Therapy and Immunity: An Update
Falk‐Mahapatra, R., & Gollnick, S. O. (2020) · Photochemistry and Photobiology · doi:10.1111/php.13253 · Cited by 195 · see citing works
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Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy
Medrano, R. F. V., Hunger, A., Mendonça, S. A., Barbuto, J. A. M., & Strauss, B. E. (2017) · Oncotarget · doi:10.18632/oncotarget.19531 · Cited by 185 · see citing works
Necroptosis in Immuno-Oncology and Cancer Immunotherapy
Sprooten, J., Wijngaert, P. D., Vanmeerbeek, I., Martin, S., Vangheluwe, P., Schlenner, S., Krysko, D. V., Parys, J. B., Bultynck, G., Vandenabeele, P., et al. (2020) · Cells · doi:10.3390/cells9081823 · Cited by 169 · see citing works
Self-citationCurrent Challenges and Opportunities of Photodynamic Therapy against Cancer
Huis in ‘t Veld, R. V., Heuts, J., Ma, S., Cruz, L. J., Ossendorp, F. A., & Jager, M. J. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020330 · Cited by 159 · see citing works
Research progress on morphology and mechanism of programmed cell death
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Trial watch: dendritic cell vaccination for cancer immunotherapy
Sprooten, J., Ceusters, J., Coosemans, A., Agostinis, P., Vleeschouwer, S. D., Zitvogel, L., Kroemer, G., Galluzzi, L., & Garg, A. D. (2019) · OncoImmunology · doi:10.1080/2162402x.2019.1638212 · Cited by 148 · see citing works
Self-citationNath, S., Obaid, G., & Hasan, T. G. (2019) · Photochemistry and Photobiology · doi:10.1111/php.13173 · Cited by 144 · see citing works
Endoplasmic reticulum targeted AIE bioprobe as a highly efficient inducer of immunogenic cell death
Li, J., Gao, H., Liu, R., Chen, C., Zeng, S., Liu, Q., & Ding, D. (2020) · Science China Chemistry · doi:10.1007/s11426-020-9846-4 · Cited by 142 · see citing works
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Type I interferons and dendritic cells in cancer immunotherapy
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Self-citationImmunogenic Apoptosis as a Novel Tool for Anticancer Vaccine Development
Montico, B., Nigro, A., Casolaro, V., & Col, J. D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020594 · Cited by 128 · see citing works
PPARG-mediated ferroptosis in dendritic cells limits antitumor immunity
Han, L., Bai, L., Qu, C., Dai, E., Liu, J., Kang, R., Zhou, D., Tang, D., & Zhao, Y. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.08.082 · Cited by 128 · see citing works
Photo-activated chemo-immunotherapy for metastatic cancer using a synergistic graphene nanosystem
Zhou, F., Wang, M., Luo, T., Qu, J., & Chen, W. R. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120421 · Cited by 124 · see citing works
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Self-citationPhotodynamic therapy with redaporfin targets the endoplasmic reticulum and Golgi apparatus
Gomes-da-Silva, L. C., Zhao, L., Bezu, L., Zhou, H., Sauvat, A., Liu, P., Durand, S., Leduc, M., Souquère, S., Loos, F., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201798354 · Cited by 118 · see citing works
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Trial watch: Dendritic cell-based anticancer immunotherapy
Garg, A. D., Vara‐Pérez, M., Schaaf, M. B. E., Agostinis, P., Zitvogel, L., Kroemer, G., & Galluzzi, L. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1328341 · Cited by 117 · see citing works
Self-citationTherapeutic cancer vaccines: From initial findings to prospects
Song, Q., Zhang, C.-D., & Wu, X.-H. (2018) · Immunology Letters · doi:10.1016/j.imlet.2018.01.011 · Cited by 106 · see citing works
The network of immunosuppressive pathways in glioblastoma
Mangani, D., Weller, M., & Roth, P. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.12.011 · Cited by 103 · see citing works
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Dendritic Cell Vaccination of Glioblastoma: Road to Success or Dead End
Datsi, A., & Sorg, R. V. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.770390 · Cited by 102 · see citing works
Radiation‐Induced Immunogenic Cell Death for Cancer Radioimmunotherapy
Liu, T., Pei, P., Shen, W., Hu, L. T., & Yang, K. (2023) · Small Methods · doi:10.1002/smtd.202201401 · Cited by 100 · see citing works
Trial watch: chemotherapy-induced immunogenic cell death in oncology
Sprooten, J., Laureano, R. S., Vanmeerbeek, I., Govaerts, J., Naulaerts, S., Borràs, D., Kinget, L., Fucikova, J. P., Špíšek, R., Jelinkova, L. P., et al. (2023) · OncoImmunology · doi:10.1080/2162402x.2023.2219591 · Cited by 100 · see citing works
Self-citationDecoding immunogenic cell death from a dendritic cell perspective
Janssens, S., Rennen, S., & Agostinis, P. (2023) · Immunological Reviews · doi:10.1111/imr.13301 · Cited by 101 · see citing works
Self-citationDendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity
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Engineering challenges for brain tumor immunotherapy
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Boosting Tumor-Specific Immunity Using PDT
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Cancer photo-immunotherapy: from bench to bedside
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Advances in immunotherapeutic research for glioma therapy
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Glioblastoma vaccines: past, present, and opportunities
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Type I interferons and endoplasmic reticulum stress in health and disease
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Fluorine assembly nanocluster breaks the shackles of immunosuppression to turn the cold tumor hot
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Cytomegalovirus promotes murine glioblastoma growth via pericyte recruitment and angiogenesis
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Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species
Zhang, Z., Wang, K., Mo, J., Xiong, L., & Wen, Y. (2020) · World Journal of Stem Cells · doi:10.4252/wjsc.v12.i7.562 · Cited by 78 · see citing works
DAMP—Induced Allograft and Tumor Rejection: The Circle Is Closing
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Current advances in temozolomide encapsulation for the enhancement of glioblastoma treatment
Iturrioz-Rodríguez, N., Samprón, N., & Matheu, A. (2023) · Theranostics · doi:10.7150/thno.82005 · Cited by 77 · see citing works
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Self-citationImmunogenic cell death and its therapeutic or prognostic potential in high-grade glioma
Decraene, B., Yang, Y., Smet, F. D., Garg, A. D., Agostinis, P., & Vleeschouwer, S. D. (2022) · Genes and Immunity · doi:10.1038/s41435-021-00161-5 · Cited by 70 · see citing works
Self-citationStrategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma
Hargadon, K. M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01594 · Cited by 68 · see citing works
Nie, D., Ling, Y., Lv, W., Liu, Q., Deng, S., Shi, J., Yang, J., Yang, Y., Ouyang, S., Huang, Y., et al. (2023) · ACS Nano · doi:10.1021/acsnano.3c03696 · Cited by 65 · see citing works
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Strategies for developing and optimizing cancer vaccines
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Stepanenko, A. A., & Chekhonin, V. P. (2018) · Cancers · doi:10.3390/cancers10120492 · Cited by 60 · see citing works
Molecular determinants of immunogenic cell death elicited by radiation therapy
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Cancer vaccines: platforms and current progress
Lei, W., Zhou, K., Lei, Y., Qiu, L., & Zhu, H. (2025) · Molecular Biomedicine · doi:10.1186/s43556-024-00241-8 · Cited by 62 · see citing works
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Natural compound inducers of immunogenic cell death
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Self-citationPhytochemicals Approach for Developing Cancer Immunotherapeutics
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Synthetic lethality between VPS4A and VPS4B triggers an inflammatory response in colorectal cancer
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Clinical implication of cellular vaccine in glioma: current advances and future prospects
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Jiang, Q., Zhang, C., Wang, H., Peng, T., Li, Z., Wang, Y., Han, W., & Shi, C. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01196 · Cited by 55 · see citing works
Hypericin: A natural anthraquinone as promising therapeutic agent
Wu, J., Zhang, J., Xia, C., Ding, K., Li, X., Pan, X.-G., Xu, J., He, J., & Zhang, W. K. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.154654 · Cited by 54 · see citing works
- Authors
- Garg, A. D., Vandenberk, L., Koks, C., Verschuere, T., Boon, L., Van Gool, S. W., & Agostinis, P.
- Affiliations
- KU Leuven (BE)
- EPIRUS Biopharmaceuticals Netherlands BV, 3584 Utrecht, Netherlands.
- Laboratory of Pediatric Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven 3000, Belgium.
- Corresponding author
- Garg, Abhishek D.
- Vandenberk, Lien
- Agostinis, Patrizia
- Venue
- Science Translational Medicine
- Published
- 2016-03-02
- Volume
- 8
- Issue
- 328
- Pages
- 328ra27-328ra27
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- OpenAlex
- W2292411590
- Cited by
- 270
- References
- 83
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 21 · 2023: 36 · 2022: 34 · 2021: 20 · 2020: 34 · 2019: 24 · 2018: 28 · 2017: 33 · 2016: 15
- FWCI
- 20.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Funders
- FWO (Fonds Wetenschappelijk Onderzoek)
- IWT (Innovatie door Wetenschap en Technologie)
- FWO (G0584.12N, K202313N, GA01111N)
- KU Leuven (C16/15/073)
- Olivia Hendrickx Research Fund
- James E. Kearney Memorial Fund
- Herman Memorial Research Fund
- Belgian Brain Tumor Support
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- dendritic cell vaccine, immunogenic cell death, high-grade glioma, glioblastoma, photodynamic therapy, hypericin, damage-associated molecular patterns, reactive oxygen species, MyD88 signaling, CD8+ T cells, temozolomide, tumor immunosuppression, regulatory T cells, cytotoxic T lymphocytes, Th17 cells, prognosis, immunotherapy
- MeSH terms
- Animals, Anthracenes, Brain Neoplasms, Dendritic Cells, Glioma, Mice, Inbred C57BL, Perylene, Photochemotherapy, T-Lymphocytes, Cytotoxic, Cell Death, Apoptosis, Reactive Oxygen Species, CD8-Positive T-Lymphocytes, Cancer Vaccines, Mice, Adaptive Immunity, Endoplasmic Reticulum Stress, Neoplasm Grading
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