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Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids
Open accessAbstract
Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means by which to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.
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“In addition, ex vivo coculture systems utilizing human peripheral blood mononuclear cells or tumor-infiltrating lymphocytes cocultured with patient-derived organoids provide valuable platforms to interrogate human-specific immune responses to phage-delivered antigens or immunotherapies [111–113]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [112]
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Cites
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895 · cited 3×
“REAGENT or RESOURCE SOURCE IDENTIFIER Somatic Indel Detector (GATK) McKenna et al., 2010 https://software.broadinstitute.org/gatk/ snpEff, version 4.3 Cingolani et al., 2012 http://snpeff.sourceforge.net FlowJo version 10 https://www.flowjo.com/ ImageJ version 1.50i Schneider et al., 2012 https://imagej.nih.gov/ij/”
InfluentialAdverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
Cingolani, P., Platts, A., Wang, L. L., Coon, M., Nguyen, T., Wang, L., Land, S. J., Lu, X., & Ruden, D. M. (2012) · Fly · doi:10.4161/fly.19695 · Cited by 11,816
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660
Self-citationPD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335 · cited 2×
“, 2012) and response to PD-1/PD-L1 blockade is restricted to approximately 20% of patients (Garon et al., 2015; Borghaei et al., 2015).”
Comprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157 · cited 1×
“The use of antibodies against immune checkpoints, such as CTLA-4 and PD-1/PD-L1, has shown clear clinical benefit for patients with advanced cancer, including melanoma, nonsmall-cell lung cancer (NSCLC), and mismatch repair-deficient (dMMR) colorectal cancer (CRC) (Larkin et al., 2015; Garon et al., 2015; Borghaei et…”
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Molecular classification of hormone receptor-positive HER2-negative breast cancer
Jin, X., Zhou, Y.-F., Ma, D., Zhao, S., Lin, C., Xiao, Y., Fu, T., Liu, C., Chen, Y., Xiao, W.-X., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01507-7 · Cited by 118
Zou, F., Tan, J., Liu, T., Liu, B., Tang, Y., Zhang, H., & Li, J. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.01.021 · Cited by 120
“To test whether CD39 also identified effector function in tumor-reactive CD8 T cells, HCC organoids were generated and co-cultured with autologous PBMCs, as previously described.(16) Co-stimulation signals were sustained to support T cells proliferation by interleukin-2 (IL-2), anti-CD28, and anti-PD-1 antibodies (Abs…”
BackgroundMethodResultInfluentialCurrent concepts in tumour-derived organoids
Porter, R. J., Murray, G. I., & McLean, M. H. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0993-5 · Cited by 125
Picco, G., Cattaneo, C. M., van Vliet, E. J., Crisafulli, G., Rospo, G., Consonni, S., Vieira, S. F., Sánchez-Rodríguez, I., Cancelliere, C., Banerjee, R., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1508 · Cited by 112
“co-cultured as previously described (39,40).”
InfluentialSelf-citationFunctional precision oncology using patient-derived assays: bridging genotype and phenotype
van Renterghem, A. W. J., van de Haar, J., & Voest, E. E. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00745-2 · Cited by 121
Self-citation3D and organoid culture in research: physiology, hereditary genetic diseases and cancer
Suarez-Martinez, E., Suazo-Sanchez, I., Celis-Romero, M., & Carnero, A. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00775-w · Cited by 118
Yu, L., Li, Z., Mei, H., Li, W., Chen, D., Liu, L., Zhang, Z., Sun, Y., Song, F., Chen, W., et al. (2021) · Clinical & Translational Immunology · doi:10.1002/cti2.1248 · Cited by 113
“expanded the tumor-reactive T cells via continuous co-cultivation of peripheral blood lymphocytes with tumor organoids, and verified the anticancer properties of those tumor specific T cells.(33) Further research on the BCO-immune cell co-culture”
BackgroundHolokai, L. L., Chakrabarti, J. L., Lundy, J., Croagh, D. G., Adhikary, P., Richards, S. S., Woodson, C., Steele, N. G., Kuester, R. K., Scott, A. J., et al. (2020) · Cancers · doi:10.3390/cancers12123816 · Cited by 110
“Similar methods have been used in autologous non-small-cell lung and colorectal cancer organoid/peripheral blood lymphocyte co-cultures [14].”
MethodZhou, G., Lieshout, R., van Tienderen, G. S., de Ruiter, V., van Royen, M. E., Boor, P. P. C., Magré, L., Desai, J., Köten, K., Kan, Y. Y., et al. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-01839-x · Cited by 110
“with allogeneic T cells [18], autologous peripheral blood mononuclear cells (PBMCs) [19], and autologous CD8 T cells and dendritic cells [20], rectal cancer with autologous tumourinfiltrating lymphocytes (TILs) [21], and non-small cell lung cancer and colorectal cancer co-cultured with T cells [22].”
Background3D models in the new era of immune oncology: focus on T cells, CAF and ECM
Modugno, F. D., Colosi, C., Trono, P., Antonacci, G., Ruocco, G., & Nisticò, P. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1086-2 · Cited by 115
“from NSCLC and colorectal cancer (CRC) patients [140].”
Seidlitz, T., Koo, B., & Stange, D. E. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00662-2 · Cited by 112
Cancer organoid co-culture model system: Novel approach to guide precision medicine
Yuan, J., Li, X., & Yu, S. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1061388 · Cited by 114
Zhou, Z., Van der Jeught, K., Fang, Y., Yu, T., Li, Y., Ao, Z., Liu, S., Zhang, L., Yang, Y., Eyvani, H., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00805-x · Cited by 107
Assembloid models of cell-cell interaction to study tissue and disease biology
Onesto, M. M., Kim, J.-I., & Pasca, S. P. (2024) · Cell Stem Cell · doi:10.1016/j.stem.2024.09.017 · Cited by 107
Modeling Cell Communication in Cancer With Organoids: Making the Complex Simple
Fiorini, E., Veghini, L., & Corbo, V. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00166 · Cited by 107
Organoids for Functional Precision Medicine in Advanced Pancreatic Cancer
Boilève, A., Cartry, J., Goudarzi, N., Bedja, S., Mathieu, J. R. R., Bani, M. A., Nicolle, R., Mouawia, A., Bouyakoub, R., Nicotra, C., et al. (2024) · Gastroenterology · doi:10.1053/j.gastro.2024.05.032 · Cited by 103
den Bossche, V. V., Zaryouh, H., Vara-Messler, M., Vignau, J., Machiels, J., Wouters, A., Schmitz, S., & Corbet, C. (2022) · Drug Resistance Updates · doi:10.1016/j.drup.2022.100806 · Cited by 105
Zou, Z., Lin, Z., Wu, C., Tan, J., Zhang, J., Peng, Y., Zhang, K., Li, J., Wu, M., & Zhang, Y. (2023) · Advanced Science · doi:10.1002/advs.202302640 · Cited by 102
Glioblastoma Organoids: Pre-Clinical Applications and Challenges in the Context of Immunotherapy
Klein, E., Hau, A., Oudin, A., Golebiewska, A., & Niclou, S. P. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.604121 · Cited by 102
“Promising results with ex vivo co-cultures of organoids with autologous PBMCshave been reported for non-small cell lung cancer and colorectal cancer (107, 108).”
BackgroundMethodInfluentialZhao, Y., Li, S., Zhu, L., Huang, M., Xie, Y., Song, X., Chen, Z., Lau, H. C.-H., Sung, J. J.-Y., Xu, L., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101627 · Cited by 113
“37 In conclusion, we established a collection of patient-derived GC organoids that retain the structural and functional characteristics of their originated tumors.”
Tumor organoid-immune co-culture models: exploring a new perspective of tumor immunity
Wang, J., Tao, X., Zhu, J., Dai, Z., Du, Y., Xie, Y., Chu, X., Fu, G., & Lei, Z. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02407-x · Cited by 101
“Moreover, their work established a methodology to evaluate the sensitivity of tumor cells to T cell-mediated attacks at an individualized patient level [5].”
Corso, S., Isella, C., Bellomo, S. E., Apicella, M., Durando, S., Migliore, C., Ughetto, S., D’Errico, L., Menegon, S., Moya-Rull, D., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-1166 · Cited by 99
Mimicking tumor hypoxia and tumor-immune interactions employing three-dimensional in vitro models
Bhattacharya, S., Calar, K., & de la Puente, P. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01583-1 · Cited by 106
The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update
Azar, J. H., Bahmad, H. F., Daher, D., Moubarak, M. M., Hadadeh, O., Monzer, A., Bitar, S. A., Jamal, M., Al‐Sayegh, M., & Abou-Kheir, W. G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147667 · Cited by 106
“This study showed that enriched population can be used in a personalized manner to kill matched tumor organoids [10].”
BackgroundSensitive identification of neoantigens and cognate TCRs in human solid tumors
Arnaud, M., Chiffelle, J., Genolet, R., Rodrigo, B. N., Perez, M. A. S., Huber, F., Magnin, M., Nguyen‐Ngoc, T., Guillaume, P., Baumgaertner, P., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-01072-6 · Cited by 99
Patient-derived organoids: a promising model for personalized cancer treatment
Yang, H., Sun, L., Liu, M., & Mao, Y. (2018) · Gastroenterology report · doi:10.1093/gastro/goy040 · Cited by 97
Biologically inspired approaches to enhance human organoid complexity
Holloway, E. M., Capeling, M. M., & Spence, J. R. (2019) · Development · doi:10.1242/dev.166173 · Cited by 99
“In addition, primary tissue-derived organoids are being used to study tumor microenvironments and cancer immunotherapies (Dijkstra et al., 2018; Neal et al., 2018).”
BackgroundAirway and alveolar epithelial cells in culture
Hiemstra, P. S., Tetley, T. D., & Janes, S. M. (2019) · European Respiratory Journal · doi:10.1183/13993003.00742-2019 · Cited by 94
Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research
Düzağaç, F., Saorin, G., Memeo, L., Canzonieri, V., & Rizzolio, F. (2021) · Cancers · doi:10.3390/cancers13040737 · Cited by 97
“developed a personalized patient model of a co-culture system that is able to induce the tumor-specific T cell response [80].”
BackgroundThe Emerging Role of YAP/TAZ in Tumor Immunity
Pan, Z., Tian, Y., Cao, C., & Niu, G. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0375 · Cited by 99
“Besides, it is noteworthy that T cells are both essential and indispensable for tumor immunology, including immune evasion by cancers and antitumor immune responses (62, 63).”
BackgroundThe tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture
Blasio, S. D., van Wigcheren, G. F., Becker, A. M. D., van Duffelen, A., Gorris, M. A. J., Verrijp, K. N., Stefanini, I., Bakker, G., Bloemendal, M., Halilović, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16583-0 · Cited by 99
Yao, Q., Cheng, S., Pan, Q., Yu, J., Cao, G., Li, L., & Cao, H. (2024) · MedComm · doi:10.1002/mco2.735 · Cited by 100
“Voest et al. 231,232 developed a tumor organoid-T cell coculture system using non-small cell lung cancer and CRC organoids to assess T cell effector functions (including interferon γ secretion and degranulation) and their ability to kill tumor organoids.”
BackgroundKim, S. K., Kim, Y. H., Park, S., & Cho, S. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.03.002 · Cited by 96
Choi, Y.-M., Lee, H., Ann, M., Song, M., Rheey, J., & Jang, J. (2023) · Biofabrication · doi:10.1088/1758-5090/acd95f · Cited by 94
Engineering approaches for studying immune-tumor cell interactions and immunotherapy
Shelton, S. E., Nguyen, H. T., Barbie, D. A., & Kamm, R. D. (2021) · iScience · doi:10.1016/j.isci.2020.101985 · Cited by 93
“To study tumor-immune interactions in patient-derived organoid models, some groups have used cancer types more likely to contain immune cells, such as mismatch repair deficient and microsatellite-unstable colorectal carcinomas (Dijkstra et al., 2018; Vellinga et al., 2016).”
BackgroundCytotoxic CD8+ Lymphocytes in the Tumor Microenvironment
Iwahori, K. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-35723-8_4 · Cited by 102
Immunotherapy of Glioblastoma: Current Strategies and Challenges in Tumor Model Development
Majc, B., Novak, M., Kopitar‐Jerala, N., Jewett, A., & Breznik, B. (2021) · Cells · doi:10.3390/cells10020265 · Cited by 98
“[147] enriched tumor-reactive T cells by co-culturing PBMCs and tumor organoids from colorectal and non-small-cell lung cancer and demonstrated that these T cells can be used to assess the efficiency of killing tumor organoids.”
Background3D cancer models: One step closer to in vitro human studies
Manduca, N., Maccafeo, E., Maria, R. D., Sistigu, A., & Musella, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1175503 · Cited by 103
Patient-derived cell line, xenograft and organoid models in lung cancer therapy
Huo, K.-G., D’Arcangelo, E., & Tsao, M. (2020) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-154 · Cited by 98
Multiple low dose therapy as an effective strategy to treat EGFR inhibitor-resistant NSCLC tumours
Neto, J. M. F., Nadal, E., Bosdriesz, E., Ooft, S., Farré, L., McLean, C. M., Klarenbeek, S., Jurgens, A. P., Hagen, H., Wang, L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16952-9 · Cited by 94
Self-citationQu, S., Xu, R., Yi, G., Li, Z., Zhang, H., Qi, S., & Huang, G. (2024) · Molecular Biomedicine · doi:10.1186/s43556-023-00165-9 · Cited by 106
“Firstly, the organoid technology lacked standardized protocols for organoid construction and operation [194–196].”
Genetics of Hepatocellular Carcinoma: Approaches to Explore Molecular Diversity
Caruso, S., O’Brien, D. R., Cleary, S. P., Roberts, L. R., & Zucman‐Rossi, J. (2020) · Hepatology · doi:10.1002/hep.31394 · Cited by 96
Zhang, S., Iyer, S., Ran, H., Dolgalev, I., Gu, S. S., Wei, W., Foster, C., Loomis, C. A., Olvera, N., Dao, F., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0455 · Cited by 89
Meng, Q., Xie, S., Gray, G. K., Dezfulian, M. H., Gandarilla, O., Li, W., Huang, L., Akshinthala, D., Ferrer, E., Conahan, C., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003213 · Cited by 90
Base editing screens map mutations affecting interferon-γ signaling in cancer
Coelho, M. A., Cooper, S., Strauß, M. E., Karakoç, E., Bhosle, S. G., Gonçalves, E., Picco, G., Burgold, T., Cattaneo, C. M., Veninga, V., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2022.12.009 · Cited by 94
Self-citationSubtil, B., Iyer, K. K., Poel, D., Bakkerus, L., Gorris, M. A. J., Cuenca‐Escalona, J., van den Dries, K., Cambi, A., Verheul, H. M. W., de Vries, I. J. M., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1105244 · Cited by 94
Current Status of Patient-Derived Ovarian Cancer Models
Maru, Y., & Hippo, Y. (2019) · Cells · doi:10.3390/cells8050505 · Cited by 92
Organoid Models for Precision Cancer Immunotherapy
Sun, C., Lan, H., Fang, X., Yang, X., & Jin, K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.770465 · Cited by 90
“This method, co-culture of immune cells and human tumor organoids, is also used for the generation of tumor-reactive T cells from autologous peripheral blood lymphocytes (33) and survey on the Helicobacter pylori infection process (34, 70).”
MethodMapping and modeling human colorectal carcinoma interactions with the tumor microenvironment
Li, N., Zhu, Q., Tian, Y., Ahn, K. J., Wang, X., Cramer, Z., Jou, J., Folkert, I. W., Yu, P., Adams‐Tzivelekidis, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43746-6 · Cited by 93
“Recent studies indicate that patient-derived tumoroids can successfully predict response to radio-and chemotherapies 5 – 10 , and tumoroids have been employed to study the development of tumor-reactive T cells 46 or the response to immune checkpoint inhibitors in coculture systems 11 .”
Complex in vitro model: A transformative model in drug development and precision medicine
Wang, L., Hu, D., Xu, J., Hu, J., & Wang, Y. (2023) · Clinical and Translational Science · doi:10.1111/cts.13695 · Cited by 87
Wang, Q., Yuan, F., Zuo, X., & Li, M. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02505-w · Cited by 101
Bai, X., Shao, J., Zhou, S., Zhao, Z., Li, F., Xiang, R., Zhao, A. Z., & Pan, J. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1478-3 · Cited by 85
“Although the current combinatorial immunotherapy has become one of the primary treatment modality for NSCLC, the response rates are still below 30% [27].”
BackgroundZhu, J., Ji, L., Chen, Y., Li, H., Huang, M., Dai, Z., Wang, J., Xiang, D., Fu, G., Lei, Z., et al. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01354-9 · Cited by 92
“In four of eight major histocompatibility complex (MHC) class I+ colorectal organoids, CD8 T cells showed tumor-specific responses but not in MHC class I deficient organoids [100].”
BackgroundInfluentialDomblides, C., Rochefort, J., Riffard, C., Panouillot, M., Lescaille, G., Teillaud, J., Mateo, V., & Dieu‐Nosjean, M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.698604 · Cited by 85
“However, a recent study has shown that the co-culture of tumor organoids (derived from CRC and NSCLC tumors) with autologous PBMC can generate tumorreactive T cells (106).”
BackgroundRole of Patient-Derived Models of Cancer in Translational Oncology
Idrisova, K., Simon, H., & Gomzikova, M. O. (2022) · Cancers · doi:10.3390/cancers15010139 · Cited by 84
“The authors proposed to use this co-culture system with tumor organoids to expand patient-specific tumor-reactive T cells as an anticancer adoptive cell therapy [78].”
BackgroundFine-Needle Aspiration-Based Patient-Derived Cancer Organoids
Vilgelm, A. E., Bergdorf, K. N., Wolf, M. M., Bharti, V., Shattuck-Brandt, R. L., Blevins, A., Jones, C. Y., Phifer, C. J., Lee, M. A., Lowe, C. L., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101408 · Cited by 78
“…for immune-containing organoids in the literature are quite complex and often recommendWnt3A-containing or cytokine supplemented media (Chakrabarti et al., 2018; Dijkstra et al., 2018; Finnberg et al., 2017; Jenkins et al., 2018; Long et al., 2014; Schnalzger et al., 2019; Seino et al., 2018).”
Background3D Culture Systems for Exploring Cancer Immunology
Fitzgerald, A. A., Li, E., & Weiner, L. M. (2020) · Cancers · doi:10.3390/cancers13010056 · Cited by 85
Newly developed 3D in vitro models to study tumor–immune interaction
Mu, P., Zhou, S., Lv, T., Xia, F., Shen, L., Wan, J., Wang, Y., Zhang, H., Cai, S., Peng, J., et al. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02653-w · Cited by 87
“In addition, they may carry unknown pathogens or other immunogenic components that may not only affect the growth of tumor organoids, but may also lead to non-specific activation of immune cells in the presence of immune components in the model, thus affecting the stability of the in vitro simulated -TME [26].”
BackgroundMethodInfluentialClinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions
Macı́as, R. I. R., Cardinale, V., Kendall, T. J., Avila, M. A., Guido, M., Coulouarn, C., Braconi, C., Frampton, A. E., Bridgewater, J. A., Overi, D., et al. (2022) · Gut · doi:10.1136/gutjnl-2022-327099 · Cited by 81
Applications of human organoids in the personalized treatment for digestive diseases
Wang, Q., Guo, F., Jin, Y., & Ma, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01194-6 · Cited by 87
“Organoid models of immunotherapy are slowly being built to support immune cell survival and study interactions between T cells and tumor cells.(415,418) The type and source of immune cells included in the coculture can be determined according to the research scenario, for example, autologous/exogenous expanded periphe…”
BackgroundDruggable genome and precision medicine in cancer: current challenges
Dupont, C., Riegel, K., Pompaiah, M., Juhl, H. H., & Rajalingam, K. (2021) · FEBS Journal · doi:10.1111/febs.15788 · Cited by 83
Immune organoids: from tumor modeling to precision oncology
Dao, V. A., Yuki, K., Lo, Y., Nakano, M., & Kuo, C. J. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.06.001 · Cited by 80
Multi-Omics Profiling of the Tumor Microenvironment: Paving the Way to Precision Immuno-Oncology
Finotello, F., & Eduati, F. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00430 · Cited by 77
Patient derived organoids in prostate cancer: improving therapeutic efficacy in precision medicine
Pamarthy, S., & Sabaawy, H. E. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01426-3 · Cited by 76
Harnessing epithelial-mesenchymal plasticity to boost cancer immunotherapy
Gu, Y., Zhang, Z., & ten Dijke, P. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-00980-8 · Cited by 78
Zhou, Z., Pang, Y., Ji, J., He, J., Liu, T., Ouyang, L., Zhang, W., Zhang, X., Zhang, Z., Zhang, K., et al. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00896-4 · Cited by 79
Ruiz-Garcia, H. J., Alvarado-Estrada, K., Schiapparelli, P. V., Quiñones‐Hinojosa, A., & Trifiletti, D. M. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.558381 · Cited by 76
“…patient therapeutic responses, there is still room for improvement, and as we have previously described, cocultured PDO or in situ glioma development in cerebral organoids has been engineered to include non-tumor TME cells such as immune cells (Dijkstra et al., 2018; Neal et al., 2018).”
BackgroundPimentel, V. O., Yaromina, A., Marcus, D., Dubois, L. J., & Lambin, P. (2020) · Journal of Immunological Methods · doi:10.1016/j.jim.2020.112899 · Cited by 75
The importance of being CAFs (in cancer resistance to targeted therapies)
Rizzolio, S., Giordano, S., & Corso, S. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02524-w · Cited by 75
“0’) have been recently developed and recapitulate TME diversity, offering great promise for in vitro modelling of personalized immunotherapy [39, 40].”
T Cell Based Immunotherapy for Cancer: Approaches and Strategies
Want, M. Y., Bashir, Z., & Najar, R. A. (2023) · Vaccines · doi:10.3390/vaccines11040835 · Cited by 79
3D tumor cultures for drug resistance and screening development in clinical applications
Peng, Z., Lv, X., Sun, H., Zhao, L., & Huang, S. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02281-2 · Cited by 77
From 2D to 3D and beyond: the evolution and impact of in vitro tumor models in cancer research
Rauner, G., Gupta, P. B., & Kuperwasser, C. (2025) · Nature Methods · doi:10.1038/s41592-025-02769-1 · Cited by 82
“Combining an air–liquid interface (ALI) with PDOs to include gastrointestinal tumor epithelia along with native immune cells could successfully preserve the original tumor T cell antigen receptor spectrum in 3D, allowing for modeling immune checkpoint blockade 118,119 .”
RIP3-dependent necroptosis contributes to the pathogenesis of chronic obstructive pulmonary disease
Chen, D., Gregory, A. D., Li, X., Wei, J., Burton, C. L., Gibson, G. A., Scott, S., Croix, C. M. S., Zhang, Y., & Shapiro, S. D. (2021) · JCI Insight · doi:10.1172/jci.insight.144689 · Cited by 72
Organoid technology in cancer precision medicine
Xia, X., Li, F., He, J., Aji, R., & Gao, D. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.04.039 · Cited by 72
Ling, A. L., & Huang, R. S. (2020) · Nature Communications · doi:10.1038/s41467-020-19563-6 · Cited by 72
Targeting stemness of cancer stem cells to fight colorectal cancers
Du, L., Cheng, Q., Zheng, H., Liu, J., Liu, L., & Chen, Q. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.02.012 · Cited by 73
Revolutionizing immune research with organoid-based co-culture and chip systems
Papp, D., Korcsmáros, T., & Hautefort, I. (2024) · Clinical & Experimental Immunology · doi:10.1093/cei/uxae004 · Cited by 74
“This platform was successfully used for assessing the efficiency of T-cell mediated tumour cell killing [17].”
MethodMicrofluidics guided by deep learning for cancer immunotherapy screening
Ao, Z., Cai, H., Wu, Z., Hu, L., Nunez, A., Zhou, Z., Liu, H., Bondesson, M., Lu, X., Lü, X., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2214569119 · Cited by 71
“T cells based on the cytotoxicity and proliferation of T cells (14).”
BackgroundAdvances in colon cancer research: in vitro and animal models
Lannagan, T. R. M., Jackstadt, R., Leedham, S. J., & Sansom, O. J. (2021) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.12.003 · Cited by 74
“To circumvent this limitation, co-culture systems of organoids with mesenchymal cells and lymphocytes have been developed [27,28].”
BackgroundGopal, S., Kwon, S., Ku, B., Lee, D. W., Kim, J., & Dordick, J. S. (2021) · Communications Biology · doi:10.1038/s42003-021-02417-2 · Cited by 68
Wang, E., Xiang, K., Zhang, Y., & Wang, X.-F. (2022) · Journal of the National Cancer Center · doi:10.1016/j.jncc.2022.10.001 · Cited by 56
“51 Furthermore, applying transcriptomic profiling by RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) on PDO not only allows for assessing the similarity between PDOs and the parental tumor, 122 but also allows for investigating the inherent tumor heterogeneity.”
BackgroundMethodInfluentialWu, Q., Tian, P., He, D., Jia, Z., He, Y., Luo, W., Lv, X., Wang, Y., Zhang, P., Liang, Y., et al. (2023) · Cell Research · doi:10.1038/s41422-023-00810-6 · Cited by 73
Novel patient-derived preclinical models of liver cancer
Bresnahan, E. R., Ramadori, P., Heikenwälder, M. F., Zender, L., & Lujambio, A. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.09.028 · Cited by 69
Ahmed, N., Kadife, E., Raza, A., Short, M. K., Jubinsky, P. T., & Kannourakis, G. (2020) · Cells · doi:10.3390/cells9030719 · Cited by 69
Organoids to study immune functions, immunological diseases and immunotherapy
Ye, W., Luo, C., Li, C., Huang, J., & Liu, F. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.02.027 · Cited by 67
Patient-Derived Organoids as a Model for Cancer Drug Discovery
Rae, C. J., Amato, F., & Braconi, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073483 · Cited by 74
“Interestingly, this approach has also been utilized to generate patient-specific tumour-reactive T cells from peripheral blood lymphocytes [66], allowing the interrogation of tumour sensitivity to immunotherapy.”
MethodSui, Q., Liu, D., Wu, J., Tang, J., Kong, L.-H., Han, K., Liao, L., Li, Y., Ou, Q., Xiao, B., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001498 · Cited by 68
Organoids and Colorectal Cancer
Barbáchano, A., Fernández‐Barral, A., Bustamante‐Madrid, P., Prieto, I., Rodríguez-Salas, N., Larriba, M. J., & Múñoz, A. (2021) · Cancers · doi:10.3390/cancers13112657 · Cited by 74
Three-dimensional colon cancer organoids model the response to CEA-CD3 T-cell engagers
Teijeira, Á., Miguéliz, I., Garasa, S., Karanikas, V., Luri‐Rey, C., Cirella, A., Olivera, I., Cañamero, M., Álvarez, M., Ochoa, M. C., et al. (2022) · Theranostics · doi:10.7150/thno.63359 · Cited by 67
“In fact, patient- and mouse-derived organoids have been used to study tumor immunology and immunotherapy adding checkpoint inhibitors to such types of short-term cultures [14-17] and also in the study of resistance mechanisms to anti- CEA T cell engagers [18].”
Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models
Si, X., Xiao, L., Brown, C. E., & Wang, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063154 · Cited by 70
“Meanwhile, TDOs allow for the investigation of endogenous CD8+ T cell infiltrates that may have synergistic effect with CAR-mediated tumor killing [88,89].”
BackgroundJeong, S. Y., & Kang, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914609 · Cited by 74
“Dijkstra et al. [52] successfully expanded tumor-reactive T cells from paired PBMCs using microsatellite instability (MSI)-high CRC and non-small cell lung cancer (NSCLC) organoids.”
MethodOrganoid models in lung regeneration and cancer
Wang, J., Li, X., & Chen, H. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.01.030 · Cited by 67
Organoid models of glioblastoma: advances, applications and challenges.
Zhang, C., Jin, M.-Z., Zhao, J., Chen, J., & Jin, W. (2020) · PubMed Central · Cited by 66
Cherne, M. D., Sidar, B., Sebrell, T. A., Sanchez, H. S., Heaton, K., Kassama, F. J., Roe, M. M., Gentry, A. B., Chang, C. B., Walk, S. T., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.707891 · Cited by 65
Wang, W., Yuan, T., Ma, L., Zhu, Y., Bao, J., Zhao, X., Zhao, Y., Zong, Y., Zhang, Y., Yang, S., et al. (2022) · Advanced Science · doi:10.1002/advs.202105810 · Cited by 63
Retracted: Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity
Vennin, C., Cattaneo, C. M., Bosch, L., Vegna, S., Ma, X., Damstra, H. G. J., Martinovic, M., Tsouri, E., Ilić, M., Azarang, L., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.05.009 · Cited by 64
Self-citationRetractedConstructing and Deconstructing Cancers using Human Pluripotent Stem Cells and Organoids
Smith, R. C., & Tabar, V. S. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.11.012 · Cited by 62
Organoid models of the tumor microenvironment and their applications
Xia, T., Du, W., Chen, X., & Zhang, Y.-N. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16578 · Cited by 63
Durinikova, E., Buzo, K., & Arena, S. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01981-z · Cited by 61
Gong, Z., Huang, L., Tang, X., Chen, K., Wu, Z., Zhang, L., Sun, Y., Xia, Y., Chen, H., Wei, Y., et al. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202101312 · Cited by 62
Metadata
- Authors
- 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., van Rooij, N., van Leerdam, M. E., Depla, A., Smit, E. F., Hartemink, K. J., de Groot, R., Wolkers, M. C., Sachs, N., Snaebjornsson, P., Monkhorst, K., Haanen, J., Clevers, H., Schumacher, T. N., & Voest, E. E.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Slotervaartziekenhuis (NL)
- Sanquin (NL)
- University Medical Center Utrecht (NL)
- Corresponding author
- Voest, Emile E.
- ORCID
- Dijkstra, Krijn K.
- Cattaneo, Chiara M.
- Weeber, Fleur
- Chalabi, Myriam
- van de Haar, Joris
- Fanchi, Lorenzo F.
- Slagter, Maarten
- van Rooij, Nienke
- van Leerdam, Monique E.
- Smit, Egbert F.
- Hartemink, Koen J.
- de Groot, Rosa
- Wolkers, Monika C.
- Sachs, Norman
- Monkhorst, Kim
- Haanen, John
- Clevers, Hans
- Schumacher, Ton N.
- Voest, Emile E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 174
- Issue
- 6
- Pages
- 1586-1598.e12
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6558289
- OpenAlex
- W2885650843
- Cited by
- 1,135
- References
- 47
- Citations by year
- 2026: 172 · 2025: 175 · 2024: 143 · 2023: 154 · 2022: 144 · 2021: 168 · 2020: 106 · 2019: 62 · 2018: 10
- FWCI
- 37.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- NWO Gravitation Program (NWO (2012-2022)
- KWF (HUBR2014-7006)
- KWF Queen Wilhelmina (NKI 2013-6122)
- ERC AdG SENSIT
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- tumor-reactive T cells, tumor organoids, peripheral blood lymphocytes, co-culture, personalized cancer immunotherapy, non-small cell lung cancer, epithelial cancers, T cell-mediated killing
- MeSH terms
- Aged, Carcinoma, Non-Small-Cell Lung, Female, Humans, Interferon-gamma, Leukocytes, Mononuclear, Lung Neoplasms, Lymphocyte Activation, Male, Middle Aged, T-Lymphocytes, Tumor Cells, Cultured, Colorectal Neoplasms, Coculture Techniques, Cell Culture Techniques, In Vitro Techniques
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