Patient-Derived Organoids for Precision Cancer Immunotherapy
Open accessAbstract
Cancer immunotherapy has revolutionized the way tumors are treated. Nevertheless, efficient and robust testing platforms are still missing, including clinically relevant human ex vivo tumor assays that allow pretreatment testing of cancer therapies and selection of the most efficient and safe therapy for a specific patient. In the case of immunotherapy, this testing platform would require not only cancer cells, but also the tumor microenvironment, including immune cells. Here, we discuss the applications of patient-derived tumor organoid cultures and the possibilities in using complex immune–organoid cultures to provide preclinical testing platforms for precision cancer immunotherapy.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cancer organoids maintain the physiological structure and function of their source tissue and are widely used in research on tumor pathogenesis, drug development, treatment resistance, and other fields.
“Cancer organoids, which maintain the physiological structure and function of their source tissue, are widely used in research on tumor pathogenesis, drug development, treatment resistance, and other fields48,49.”
From An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer (2026) · cites this paper as [48]
The Patient-derived organoids section says tumor organoids resemble their source tissue, retain key genetic and phenotypic features, and are used to model disease progression and test drugs. The Complex organoids and immunotherapy section also describes studying resistance mechanisms, but specifically with immune-enhanced organoids. The claim overstates preservation of tissue function generally: the Complex organoids section says tumor organoids do not fully recapitulate the tumor microenvironment. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204 · see citing works
A guide to cancer immunotherapy: from T cell basic science to clinical practice
Waldman, A. D., Fritz, J. M., & Lenardo, M. J. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0306-5 · Cited by 4,154 · see citing works
Modeling Development and Disease with Organoids
Clevers, H. (2016) · Cell · doi:10.1016/j.cell.2016.05.082 · Cited by 3,196 · see citing works
Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients
van de Wetering, M., Francies, H. E., Francis, J. M., Bounova, G., Iorio, F., Pronk, A., van Houdt, W., van Gorp, J., Taylor-Weiner, A., Kester, L., et al. (2015) · Cell · doi:10.1016/j.cell.2015.03.053 · Cited by 2,408 · see citing works
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers
Vlachogiannis, G., Hedayat, S., Vatsiou, A., Jamin, Y., Fernández-Mateos, J., Khan, K., Lampis, A., Eason, K., Huntingford, I., Burke, R., et al. (2018) · Science · doi:10.1126/science.aao2774 · Cited by 2,096 · see citing works
A living biobank of breast cancer organoids captures disease heterogeneity
Sachs, N., de Ligt, J., Kopper, O., Gogola, E., Bounova, G., Weeber, F., Balgobind, A. V., Wind, K., Gracanin, A., Begthel, H., et al. (2018) · Cell · doi:10.1016/j.cell.2017.11.010 · Cited by 1,973 · see citing works
Drost, J., & Clevers, H. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0007-6 · Cited by 1,790 · see citing works
Immune evasion in cancer: mechanistic basis and therapeutic strategies
Vinay, D. S., Ryan, E. P., Pawelec, G., Talib, W. H., Stagg, J., Elkord, E., Lichtor, T., Decker, W. K., Whelan, R. L., Kumara, H. M. C. S., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.03.004 · Cited by 1,625 · cited 1× · see citing works
“Our immune system already has a complex series of mechanisms to detect and eradicate cancer cells, but many on them are inactivated during cancer progression (1).”
BackgroundOrganoid modeling of the tumor immune microenvironment
Neal, J. T., Li, X., Zhu, J., Giangarra, V., Grzeskowiak, C. L., Ju, J., Liu, I. H., Chiou, S.-H., Salahudeen, A. A., Smith, A. R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.021 · Cited by 1,556 · see citing works
Dijkstra, K. K., Cattaneo, C. M., Weeber, F., Chalabi, M., van de Haar, J., Fanchi, L. F., Slagter, M., van der Velden, D. L., Kaing, S., Kelderman, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.009 · Cited by 1,135 · see citing works
CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation
Deng, J., Wang, E. S., Jenkins, R. W., Li, S., Dries, R., Yates, K., Chhabra, S., Huang, W., Liu, H., Aref, A. R., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0915 · Cited by 770 · see citing works
3D model for CAR‐mediated cytotoxicity using patient‐derived colorectal cancer organoids
Schnalzger, T. E., de Groot, M. H., Zhang, C., Mosa, M. H., Michels, B. E., Röder, J., Darvishi, T., Wels, W. S., & Farin, H. F. (2019) · The EMBO Journal · doi:10.15252/embj.2018100928 · Cited by 354 · see citing works
Engineering Organoid Vascularization
Grebenyuk, S., & Ranga, A. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00039 · Cited by 295 · see citing works
Cross talk between cancer and immune cells: exploring complex dynamics in a microfluidic environment
Businaro, L., De Ninno, A., Schiavoni, G., Lucarini, V., Ciasca, G., Gerardino, A., Belardelli, F., Gabriele, L., & Mattei, F. (2013) · Lab Chip · doi:10.1039/c2lc40887b · Cited by 162 · see citing works
Langan, L. M., Dodd, N. J. F., Owen, S. F., Purcell, W. M., Jackson, S. K., & Jha, A. N. (2016) · PLOS ONE · doi:10.1371/journal.pone.0149492 · Cited by 101 · see citing works
Flagged first, then by citations
Research works printed but not linked: 40
- [2]Galluzzi L Vacchelli E Bravo-San Pedro JM Buque A Senovilla L Baracco EE Classification of current anticancer immunotherapies Oncotarget 2014 5 12472 508 10.18632/oncotarget.2998 25537519 PMC4350348 · DOI
- [4]Taefehshokr N Baradaran B Baghbanzadeh A Taefehshokr S Promising approaches in cancer immunotherapy Immunobiology 1979 2020 225 151875 31812343
- [5]Christofi T Baritaki S Falzone L Libra M Zaravinos A Current perspectives in cancer immunotherapy Cancers 2019 11 1472 10.3390/cancers11101472 31575023 PMC6826426 · DOI
- [6]Wan ACA Recapitulating Cell–Cell interactions for organoid construction – are biomaterials dispensable? Trends in Biotechnology 2016 34 711 21 27012157
- [9]Bleijs M Wetering M Clevers H Drost J Xenograft and organoid model systems in cancer research The EMBO journal 2019 38 e101654 n/a 10.15252/embj.2019101654 31282586 PMC6670015 · DOI · Paper page
- [11]Bray LJ Hutmacher DW Bock N Addressing patient specificity in the engineering of tumor models Frontiers in Bioengineering and Biotechnology 2019 7 217 10.3389/fbioe.2019.00217 31572718 PMC6751285 · DOI
- [12]Holloway EM Capeling MM Spence JR Biologically inspired approaches to enhance human organoid complexity Development (Cambridge, England) 2019 146 dev166173 10.1242/dev.166173 30992275 PMC6503984 · DOI
- [14]Driehuis E Kretzschmar K Clevers H Establishment of patient-derived cancer organoids for drug-screening applications Nature Protocols 2020 15 3380 409 32929210
- [16]Kim M Mun H Sung CO Cho EJ Jeon H Chun S Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening Nature communications 2019 10 3991 15 10.1038/s41467-019-11867-6 31488816 PMC6728380 · DOI · Paper page
- [17]Liu F Huang J Ning B Liu Z Chen S Zhao W Drug discovery via human-derived stem cell organoids Frontiers in pharmacology 2016 7 334 10.3389/fphar.2016.00334 27713700 PMC5032635 · DOI
- [19]Pauli C Hopkins BD Prandi D Shaw R Fedrizzi T Sboner A Personalized in vitro and in vivo cancer models to guide precision medicine Cancer discovery 2017 7 462 77 10.1158/2159-8290.CD-16-1154 28331002 PMC5413423 · DOI
- [20]Genova E Cavion F Lucafo M Leo L Pelin M Stocco G Induced pluripotent stem cells for therapy personalization in pediatric patients: Focus on drug-induced adverse events World Journal of Stem Cells 2019 11 1020 44 10.4252/wjsc.v11.i12.1020 31875867 PMC6904863 · DOI
- [21]Zumwalde NA Haag JD Sharma D Mirrielees JA Wilke LG Gould MN Analysis of immune cells from human mammary ductal epithelial organoids reveals Vδ2 + T cells that efficiently target breast carcinoma cells in the presence of bisphosphonate Cancer prevention research (Philadelphia, Pa.) 2016 9 305 16 10.1158/1940-6207.CAPR-15-0370-T 26811335 PMC4818696 · DOI
- [22]Jenkins RW Aref AR Lizotte PH Ivanova E Stinson S Zhou CW Ex vivo profiling of PD-1 blockade using organotypic tumor spheroids Cancer discovery 2018 8 196 215 10.1158/2159-8290.CD-17-0833 29101162 PMC5809290 · DOI · Paper page
- [23]Finnberg NK Gokare P Lev A Grivennikov SI MacFarlane 4 Alexander W Campbell KS Application of 3D tumoroid systems to define immune and cytotoxic therapeutic responses based on tumoroid and tissue slice culture molecular signatures Oncotarget 2017 8 66747 57 10.18632/oncotarget.19965 28977993 PMC5620133 · DOI
- [26]Tsai S McOlash L Palen K Johnson B Duris C Yang Q Development of primary human pancreatic cancer organoids, matched stromal and immune cells and 3D tumor microenvironment models BMC cancer 2018 18 335 10.1186/s12885-018-4238-4 29587663 PMC5870823 · DOI · Paper page
- [27]Holokai L Chakrabarti J Broda T Chang J Hawkins JA Sundaram N Increased programmed death-ligand 1 is an early epithelial cell response to helicobacter pylori infection PLoS pathogens 2019 15 e1007468 10.1371/journal.ppat.1007468 30703170 PMC6380601 · DOI
- [28]Hirschhaeuser F Menne H Dittfeld C West J Mueller-Klieser W Kunz-Schughart LA Multicellular tumor spheroids: An underestimated tool is catching up again Journal of Biotechnology 2010 148 3 15 20097238
- [30]Bhattacharya S Calar K de la Puente P Mimicking tumor hypoxia and tumor-immune interactions employing three-dimensional in vitro models J Exp Clin Cancer Res 2020 39 75 1 10.1186/s13046-020-01583-1 32357910 PMC7195738 · DOI
- [31]Wörsdörfer P Dalda N Kern A Krüger S Wagner N Kwok CK Generation of complex human organoid models including vascular networks by incorporation of mesodermal progenitor cells Scientific reports 2019 9 15663 13 10.1038/s41598-019-52204-7 31666641 PMC6821804 · DOI
- [32]Mansour AA Gonçalves JT Bloyd CW Li H Fernandes S Quang D An in vivo model of functional and vascularized human brain organoids Nature biotechnology 2018 36 432 41 10.1038/nbt.4127 29658944 PMC6331203 · DOI · Paper page
- [34]Nashimoto Y Hayashi T Kunita I Nakamasu A Torisawa YS Nakayama M Integrating perfusable vascular networks with a three-dimensional tissue in a microfluidic device Integrative Biology (Camb) 2017 9 506 18 28561127
- [35]Yu F Hunziker W Choudhury D Engineering microfluidic organoid-on-a-chip platforms Micromachines 2019 10 165 10.3390/mi10030165 30818801 PMC6470849 · DOI
- [36]Bhatia SN Ingber DE Microfluidic organs-on-chips Nature biotechnology 2014 32 760 72 25093883
- [38]Yuki K Cheng N Nakano M Kuo CJ Organoid models of tumor immunology Trends in immunology 2020 41 652 64 10.1016/j.it.2020.06.010 32654925 PMC7416500 · DOI
- [39]Lu R Hwang Y Liu I- Lee C Tsai H Li H Development of therapeutic antibodies for the treatment of diseases Journal of Biomedical Science 2020 27 cited May 13, 2020 10.1186/s12929-019-0592-z 31894001 PMC6939334 · DOI
- [40]Chakrabarti J Holokai L Syu L Steele NG Chang J Wang J Hedgehog signaling induces PD-L1 expression and tumor cell proliferation in gastric cancer Oncotarget 2018 9 37439 57 10.18632/oncotarget.26473 30647844 PMC6324774 · DOI
- [42]Courau T Bonnereau J Chicoteau J Bottois H Remark R Assante Miranda L Cocultures of human colorectal tumor spheroids with immune cells reveal the therapeutic potential of MICA/B and NKG2A targeting for cancer treatment Journal for immunotherapy of cancer 2019 7 74 10.1186/s40425-019-0553-9 30871626 PMC6417026 · DOI
- [43]Labrijn AF Janmaat ML Reichert JM Parren Paul WHI Bispecific antibodies: A mechanistic review of the pipeline Nature reviews Drug discovery 2019 18 585 608 31175342
- [44]Gonzalez-Exposito R Semiannikova M Griffiths B Khan K Barber LJ Woolston A CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids Journal for immunotherapy of cancer 2019 7 101 10.1186/s40425-019-0575-3 30982469 PMC6463631 · DOI
- [45]Ylösmäki E Cerullo V Design and application of oncolytic viruses for cancer immunotherapy Current opinion in biotechnology 2019 65 25 31874424
- [46]Cerullo V Vähä-Koskela M Hemminki A Oncolytic adenoviruses Oncoimmunology 2012 1 979 81 10.4161/onci.20172 23162778 PMC3489766 · DOI
- [47]Cerullo V Pesonen S Diaconu I Escutenaire S Arstila PT Ugolini M Oncolytic adenovirus coding for granulocyte macrophage colony-stimulating factor induces antitumoral immunity in cancer patients Cancer research (Chicago, Ill) 2010 70 4297 309 20484030
- [48]Raimondi G Mato-Berciano A Pascual-Sabater S Rovira-Rigau M Cuatrecasas M Fondevila C Patient-derived pancreatic tumour organoids identify therapeutic responses to oncolytic adenoviruses EBioMedicine 2020 56 102786 10.1016/j.ebiom.2020.102786 32460166 PMC7251378 · DOI
- [49]Zhu Z Mesci P Bernatchez JA Gimple RC Wang X Schafer ST Zika virus targets glioblastoma stem cells through a SOX2-integrin alphavbeta5 axis Cell Stem Cell 2020 26 187 204 e10 10.1016/j.stem.2019.11.016 31956038 PMC9628766 · DOI
- [50]Majzner RG Mackall CL Clinical lessons learned from the first leg of the CAR T cell journey Nature medicine 2019 25 1341 55 31501612
- [51]Michie J Beavis PA Freeman AJ Vervoort SJ Ramsbottom KM Narasimhan V Antagonism of IAPs enhances CAR T-cell efficacy Cancer Immunol Res 2019 7 183 92 30651288
- [53]Badalamenti G Fanale D Incorvaia L Barraco N Listì A Maragliano R Role of tumor-infiltrating lymphocytes in patients with solid tumors: Can a drop dig a stone? Cellular immunology 2019 343 103753 29395859
- [54]Kong JCH Guerra GR Millen RM Roth S Xu H Neeson PJ Tumor-infiltrating lymphocyte function predicts response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer JCO Precision Oncology 2018 1 15 35135158
- [55]Votanopoulos KI Skardal A ASO author reflections: Co-cultured lymph node and tumor organoids as a platform for the creation of adaptive immunity and predict response to immunotherapy Annals of surgical oncology 2020 27 1968 9 32185535
Cited by
Sorted by citations
Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems
Silva-Pedrosa, R., Salgado, A. J., & Ferreira, P. E. (2023) · Cells · doi:10.3390/cells12060930 · Cited by 84 · see citing works
Cheng, C., Sun, L., Yang, J., Liu, Z., Zhang, F., Qiu, L., Yu, M., Wang, T., Huang, J., Wang, L., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-73682-0
- Authors
- Grönholm, M., Feodoroff, M., Antignani, G., Martins, B., Hamdan, F., & Cerullo, V.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Cerullo, Vincenzo
- ORCID
- Venue
- Cancer Research
- Published
- 2021-03-09
- Volume
- 81
- Issue
- 12
- Pages
- 3149-3155
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC7616950
- OpenAlex
- W3133726036
- Cited by
- 146
- References
- 15
- Citations by year
- 2026: 32 · 2025: 37 · 2024: 32 · 2023: 24 · 2022: 17 · 2021: 3
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Työväentutkimus Vuosikirja (submittedVersion)
- Funders
- ERC (681219)
- Jane and Aatos Erkko Foundation (4705796)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- patient-derived organoids, cancer immunotherapy, precision oncology, tumor microenvironment
- MeSH terms
- Drug Screening Assays, Antitumor, Humans, Immunotherapy, Neoplasms, Organoids, Precision Medicine, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
