AI Chat Paper
Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
(
In recent years, the three‐dimensional (3D) culture system has emerged as a promising preclinical model for tumor research owing to its ability to replicate the tissue structure and molecular characteristics of solid tumors in vivo. This system offers several advantages, including high throughput, efficiency, and retention of tumor heterogeneity. Traditional Matrigel‐submerged organoid cultures primarily support the long‐term proliferation of epithelial cells. One solution for the exploration of the tumor microenvironment is a reconstitution approach involving the introduction of exogenous cell types, either in dual, triple or even multiple combinations. Another solution is a holistic approach including patient‐derived tumor fragments, air‐liquid interface, suspension 3D culture, and microfluidic tumor‐on‐chip models. Organoid co‐culture models have also gained popularity for studying the tumor microenvironment, evaluating tumor immunotherapy, identifying predictive biomarkers, screening for effective drugs, and modeling infections. By leveraging these 3D culture systems, it is hoped to advance the clinical application of therapeutic approaches and improve patient outcomes.
Mao JJ, Pillai GG, Andrade CJ, Ligibel JA, Basu P, Cohen L, et al. Integrative oncology: addressing the global challenges of cancer prevention and treatment. CA Cancer J Clin. 2022;72(2):144–64. https://doi.org/10.3322/caac.21706
Gunti S, Hoke ATK, Vu KP, London NR. Organoid and spheroid tumor models: techniques and applications. Cancers. 2021;13(4):874. https://doi.org/10.3390/cancers13040874
American Cancer Society. Global cancer facts & figures. 4th ed. Atlanta: American Cancer Society; 2018.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660
Rodrigues T, Kundu B, Silva‐Correia J, Kundu SC, Oliveira JM, Reis RL, et al. Emerging tumor spheroids technologies for 3D in vitro cancer modeling. Pharmacol Ther. 2018;184:201–11. https://doi.org/10.1016/j.pharmthera.2017.10.018
Sachs N, Clevers H. Organoid cultures for the analysis of cancer phenotypes. Curr Opin Genet Dev. 2014;24:68–73. https://doi.org/10.1016/j.gde.2013.11.012
Bartucci M, Ferrari AC, Kim IY, Ploss A, Yarmush M, Sabaawy HE. Personalized medicine approaches in prostate cancer employing patient derived 3D organoids and humanized mice. Front Cell Dev Biol. 2016;4:64. https://doi.org/10.3389/fcell.2016.00064
Fong EL, Harrington DA, Farach‐Carson MC, Yu H. Heralding a new paradigm in 3D tumor modeling. Biomaterials. 2016;108:197–213. https://doi.org/10.1016/j.biomaterials.2016.08.052
Smith E, Cochrane WJ. Cystic organoid teratoma; report of a case. Can Med Assoc J. 1946;55(2):151.
Lancaster MA, Knoblich JA. Organogenesis in a dish: modeling development and disease using organoid technologies. Science. 2014;345(6194):1247125. https://doi.org/10.1126/science.1247125
Dutta D, Heo I, Clevers H. Disease modeling in stem cell‐derived 3D organoid systems. Trends Mol Med. 2017;23(5):393–410. https://doi.org/10.1016/j.molmed.2017.02.007
Tuveson D, Clevers H. Cancer modeling meets human organoid technology. Science. 2019;364(6444):952–5. https://doi.org/10.1126/science.aaw6985
Prigerson HG, Bao YH, Shah MA, Paulk ME, LeBlanc TW, Schneider BJ, et al. Chemotherapy use, performance status, and quality of life at the end of life. JAMA Oncol. 2015;1(6):778–84. https://doi.org/10.1001/jamaoncol.2015.2378
Miserocchi G, Mercatali L, Liverani C, de Vita A, Spadazzi C, Pieri F, et al. Management and potentialities of primary cancer cultures in preclinical and translational studies. J Transl Med. 2017;15(1):229. https://doi.org/10.1186/s12967-017-1328-z
Ooft SN, Weeber F, Dijkstra KK, McLean CM, Kaing S, van Werkhoven E, et al. Patient‐derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients. Sci Transl Med. 2019;11(513):eaay2574. https://doi.org/10.1126/scitranslmed.aay2574
Pamarthy S, Sabaawy HE. Patient derived organoids in prostate cancer: improving therapeutic efficacy in precision medicine. Mol Cancer. 2021;20(1):125. https://doi.org/10.1186/s12943-021-01426-3
Xu HX, Jiao DC, Liu AG, Wu KM. Tumor organoids: applications in cancer modeling and potentials in precision medicine. J Hematol Oncol. 2022;15(1):58. https://doi.org/10.1186/s13045-022-01278-4
Sereti E, Papapostolou I, Dimas K. Pancreatic cancer organoids: an emerging platform for precision medicine. Biomedicines. 2023;11(3):890. https://doi.org/10.3390/biomedicines11030890
Grönholm M, Feodoroff M, Antignani G, Martins B, Hamdan F, Cerullo V. Patient‐derived organoids for precision cancer immunotherapy. Cancer Res. 2021;81(12):3149–55. https://doi.org/10.1158/0008-5472
Jacob F, Salinas RD, Zhang DY, Nguyen PTT, Schnoll JG, Wong SZH, et al. A patient‐derived glioblastoma organoid model and biobank recapitulates inter‐ and intra‐tumoral heterogeneity. Cell. 2020;180(1):188–204. https://doi.org/10.1016/j.cell.2019.11.036
Dijkstra KK, Cattaneo CM, Weeber F, Chalabi M, van de Haar J, Fanchi LF, et al. Generation of tumor‐reactive T cells by co‐culture of peripheral blood lymphocytes and tumor organoids. Cell. 2018;174(6):1586–98. https://doi.org/10.1016/j.cell.2018.07.009
Cimen Bozkus C, Bhardwaj N. Tumor organoid‐originated biomarkers predict immune response to PD‐1 blockade. Cancer Cell. 2021;39(9):1187–9. https://doi.org/10.1016/j.ccell.2021.08.003
Neal JT, Li XN, Zhu JJ, Giangarra V, Grzeskowiak CL, Ju JH, et al. Organoid modeling of the tumor immune microenvironment. Cell. 2018;175(7):1972–88. https://doi.org/10.1016/j.cell.2018.11.021
Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292(5819):154–6. https://doi.org/10.1038/292154a0
Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, et al. Single Lgr5 stem cells build crypt‐villus structures in vitro without a mesenchymal niche. Nature. 2009;459(7244):262–5. https://doi.org/10.1038/nature07935
Thomson JA, Itskovitz‐Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145–7. https://doi.org/10.1126/science.282.5391.1145
Gioiella F, Urciuolo F, Imparato G, Brancato V, Netti PA. An engineered breast cancer model on a chip to replicate ECM‐activation in vitro during tumor progression. Adv Healthcare Mater. 2016;5(23):3074–84. https://doi.org/10.1002/adhm.201600772
Yuki K, Cheng N, Nakano M, Kuo CJ. Organoid models of tumor immunology. Trends Immunol. 2020;41(8):652–64. https://doi.org/10.1016/j.it.2020.06.010
Sachs N, Papaspyropoulos A, Zomer‐van Ommen DD, Heo I, Böttinger L, Klay D, et al. Long‐term expanding human airway organoids for disease modeling. EMBO J. 2019;38(4):e100300. https://doi.org/10.15252/embj.2018100300
Elyada E, Bolisetty M, Laise P, Flynn WF, Courtois ET, Burkhart RA, et al. Cross‐species single‐cell analysis of pancreatic ductal adenocarcinoma reveals antigen‐presenting cancer‐associated fibroblasts. Cancer Discov. 2019;9(8):1102–23. https://doi.org/10.1158/2159-8290.Cd-19-0094
Schnalzger TE, de Groot MH, Zhang CC, Mosa MH, Michels BE, Röder J, et al. 3D model for CAR‐mediated cytotoxicity using patient‐derived colorectal cancer organoids. EMBO J. 2019;38(12):e100928. https://doi.org/10.15252/embj.2018100928
Kong JCH, Guerra GR, Millen RM, Roth S, Xu HL, Neeson PJ, et al. Tumor‐infiltrating lymphocyte function predicts response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. JCO Precis Oncol. 2018;2:1–15. https://doi.org/10.1200/po.18.00075
Cattaneo CM, Dijkstra KK, Fanchi LF, Kelderman S, Kaing S, van Rooij N, et al. Tumor organoid–T‐cell coculture systems. Nat Protoc. 2020;15(1):15–39. https://doi.org/10.1038/s41596-019-0232-9
Zhou G, Lieshout R, van Tienderen GS, de Ruiter V, van Royen ME, Boor PPC, et al. Modelling immune cytotoxicity for cholangiocarcinoma with tumour‐derived organoids and effector T cells. Br J Cancer. 2022;127(4):649–60. https://doi.org/10.1038/s41416-022-01839-x
Cózar B, Greppi M, Carpentier S, Narni‐Mancinelli E, Chiossone L, Vivier E. Tumor‐infiltrating natural killer cells. Cancer Discov. 2021;11(1):34–44. https://doi.org/10.1158/2159-8290.cd-20-0655
Chakrabarti J, Holokai L, Syu L, Steele NG, Chang J, Wang J, et al. Hedgehog signaling induces PD‐L1 expression and tumor cell proliferation in gastric cancer. Oncotarget. 2018;9(100):37439–57. https://doi.org/10.18632/oncotarget.26473
Chakrabarti J, Holokai L, Syu L, Steele N, Chang JL, Dlugosz A, et al. Mouse‐derived gastric organoid and immune cell co‐culture for the study of the tumor microenvironment. Methods Mol Biol. 2018;1817:157–68. https://doi.org/10.1007/978-1-4939-8600-2_16
Chakrabarti J, Koh V, Steele N, Hawkins J, Ito Y, Merchant JL, et al. Disruption of Her2‐induced PD‐L1 inhibits tumor cell immune evasion in patient‐derived gastric cancer organoids. Cancers. 2021;13(24):6158. https://doi.org/10.3390/cancers13246158
Koh V, Chakrabarti J, Torvund M, Steele N, Hawkins JA, Ito Y, et al. Hedgehog transcriptional effector GLI mediates mTOR‐Induced PD‐L1 expression in gastric cancer organoids. Cancer Lett. 2021;518:59–71. https://doi.org/10.1016/j.canlet.2021.06.007
Votanopoulos KI, Forsythe S, Sivakumar H, Mazzocchi A, Aleman J, Miller L, et al. Model of patient‐specific immune‐enhanced organoids for immunotherapy screening: feasibility study. Ann Surg Oncol. 2020;27(6):1956–67. https://doi.org/10.1245/s10434-019-08143-8
Votanopoulos KI, Mazzocchi A, Sivakumar H, Forsythe S, Aleman J, Levine EA, et al. Appendiceal cancer patient‐specific tumor organoid model for predicting chemotherapy efficacy prior to initiation of treatment: a feasibility study. Ann Surg Oncol. 2019;26(1):139–47. https://doi.org/10.1245/s10434-018-7008-2
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. Ann Surg Oncol. 2020;27(6):1968–9. https://doi.org/10.1245/s10434-020-08351-7
Bar‐Ephraim YE, Kretzschmar K, Clevers H. Organoids in immunological research. Nat Rev Immunol. 2020;20(5):279–93. https://doi.org/10.1038/s41577-019-0248-y
Voabil P, de Bruijn M, Roelofsen LM, Hendriks SH, Brokamp S, van den Braber M, et al. An ex vivo tumor fragment platform to dissect response to PD‐1 blockade in cancer. Nature Med. 2021;27(7):1250–61. https://doi.org/10.1038/s41591-021-01398-3
Yi M, Jiao DC, Xu HX, Liu Q, Zhao WH, Han XW, et al. Biomarkers for predicting efficacy of PD‐1/PD‐L1 inhibitors. Mol Cancer. 2018;17(1):129. https://doi.org/10.1186/s12943-018-0864-3
Finnberg NK, Gokare P, Lev A, Grivennikov SI, MacFarlane AW 4th, Campbell KS, et al. Application of 3D tumoroid systems to define immune and cytotoxic therapeutic responses based on tumoroid and tissue slice culture molecular signatures. Oncotarget. 2017;8(40):66747–57. https://doi.org/10.18632/oncotarget.19965
Ootani A, Li X, Sangiorgi E, Ho QT, Ueno H, Toda S, et al. Sustained in vitro intestinal epithelial culture within a Wnt‐dependent stem cell niche. Nature Med. 2009;15(6):701–6. https://doi.org/10.1038/nm.1951
DiMarco RL, Su J, Yan KS, Dewi R, Kuo CJ, Heilshorn SC. Engineering of three‐dimensional microenvironments to promote contractile behavior in primary intestinal organoids. Integr Biol. 2014;6(2):127–42. https://doi.org/10.1039/c3ib40188j
Li XN, Nadauld L, Ootani A, Corney DC, Pai RK, Gevaert O, et al. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nature Med. 2014;20(7):769–77. https://doi.org/10.1038/nm.3585
Esser LK, Branchi V, Leonardelli S, Pelusi N, Simon AG, Klümper N, et al. Cultivation of clear cell renal cell carcinoma patient‐derived organoids in an air‐liquid interface system as a tool for studying individualized therapy. Front Oncol. 2020;10:1775. https://doi.org/10.3389/fonc.2020.01775
Jacob F, Ming GL, Song HJ. Generation and biobanking of patient‐derived glioblastoma organoids and their application in CAR T cell testing. Nat Protoc. 2020;15(12):4000–33. https://doi.org/10.1038/s41596-020-0402-9
Kuo CJ, Voest E, Parrini MC, Zou W, Teng MW, Greten TF, et al. Models for immuno‐oncology research. Cancer Cell. 2020;38(2):145–7. https://doi.org/10.1016/j.ccell.2020.07.010
Too NSH, Ho NCW, Adine C, Iyer NG, Fong ELS. Hot or cold: bioengineering immune contextures into in vitro patient‐derived tumor models. Adv Drug Deliv Rev. 2021;175:113791. https://doi.org/10.1016/j.addr.2021.05.001
Grebenyuk S, Ranga A. Engineering organoid vascularization. Front Bioeng Biotechnol. 2019;7:39. https://doi.org/10.3389/fbioe.2019.00039
Del Piccolo N, Shirure VS, Bi Y, Goedegebuure SP, Gholami S, Hughes CCW, et al. Tumor‐on‐chip modeling of organ‐specific cancer and metastasis. Adv Drug Deliv Rev. 2021;175:113798. https://doi.org/10.1016/j.addr.2021.05.008
Yang LB, Liu Q, Zhang XQ, Liu XW, Zhou BX, Chen JN, et al. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature. 2020;583:133–8. https://doi.org/10.1038/s41586-020-2394-6
Mehta P, Rahman Z, ten Dijke P, Boukany PE. Microfluidics meets 3D cancer cell migration. Trends Cancer. 2022;8(8):683–97. https://doi.org/10.1016/j.trecan.2022.03.006
Jenkins RW, Aref AR, Lizotte PH, Ivanova E, Stinson S, Zhou CW, et al. Ex vivo profiling of PD‐1 blockade using organotypic tumor spheroids. Cancer Discov. 2018;8(2):196–215. https://doi.org/10.1158/2159-8290.cd-17-0833
Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, et al. CDK4/6 inhibition augments antitumor immunity by enhancing T‐cell activation. Cancer Discov. 2018;8(2):216–33. https://doi.org/10.1158/2159-8290.cd-17-0915
Ao Z, Cai HW, Wu ZH, Hu LY, Li X, Kaurich C, et al. Evaluation of cancer immunotherapy using mini‐tumor chips. Theranostics. 2022;12(8):3628–36. https://doi.org/10.7150/thno.71761
Chen MB, Hajal C, Benjamin DC, Yu C, Azizgolshani H, Hynes RO, et al. Inflamed neutrophils sequestered at entrapped tumor cells via chemotactic confinement promote tumor cell extravasation. Proc Natl Acad Sci. 2018;115(27):7022–7. https://doi.org/10.1073/pnas.1715932115
Kim H, Chung H, Kim J, Choi DH, Shin Y, Kang YG, et al. Macrophages‐triggered sequential remodeling of endothelium‐interstitial matrix to form pre‐metastatic niche in microfluidic tumor microenvironment. Adv Sci. 2019;6(11):1900195. https://doi.org/10.1002/advs.201900195
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(1):75. https://doi.org/10.1186/s13046-020-01583-1
Neufeld L, Yeini E, Reisman N, Shtilerman Y, Ben‐Shushan D, Pozzi S, et al. Microengineered perfusable 3D‐bioprinted glioblastoma model for in vivo mimicry of tumor microenvironment. Sci Adv. 2021;7(34):eabi9119. https://doi.org/10.1126/sciadv.abi9119
Nguyen M, De Ninno A, Mencattini A, Mermet‐Meillon F, Fornabaio G, Evans SS, et al. Dissecting effects of anti‐cancer drugs and cancer‐associated fibroblasts by on‐chip reconstitution of immunocompetent tumor microenvironments. Cell Rep. 2018;25(13):3884–93. https://doi.org/10.1016/j.celrep.2018.12.015
Mannino RG, Santiago‐Miranda AN, Pradhan P, Qiu Y, Mejias JC, Neelapu SS, et al. 3D microvascular model recapitulates the diffuse large B‐cell lymphoma tumor microenvironment in vitro. Lab Chip. 2017;17(3):407–14. https://doi.org/10.1039/c6lc01204c
Mejías JC, Nelson MR, Liseth O, Roy K. A 96‐well format microvascularized human lung‐on‐a‐chip platform for microphysiological modeling of fibrotic diseases. Lab Chip. 2020;20(19):3601–11. https://doi.org/10.1039/d0lc00644k
Rodrigues J, Heinrich MA, Teixeira LM, Prakash J. 3D in vitro model (R)evolution: unveiling tumor‐stroma interactions. Trends Cancer. 2021;7(3):249–64. https://doi.org/10.1016/j.trecan.2020.10.009
Beghin A, Grenci G, Sahni G, Guo S, Rajendiran H, Delaire T, et al. Automated high‐speed 3D imaging of organoid cultures with multi‐scale phenotypic quantification. Nat Methods. 2022;19(7):881–92. https://doi.org/10.1038/s41592-022-01508-0
Öhlund D, Handly‐Santana A, Biffi G, Elyada E, Almeida AS, Ponz‐Sarvise M, et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J Exp Med. 2017;214(3):579–96. https://doi.org/10.1084/jem.20162024
Biffi G, Oni TE, Spielman B, Hao Y, Elyada E, Park Y, et al. IL1‐induced JAK/STAT signaling is antagonized by TGFβ to shape CAF heterogeneity in pancreatic ductal adenocarcinoma. Cancer Discov. 2019;9(2):282–301. https://doi.org/10.1158/2159-8290.Cd-18-0710
Luo XB, Fong ELS, Zhu CJ, Lin QXX, Xiong M, Li AM, et al. Hydrogel‐based colorectal cancer organoid co‐culture models. Acta Biomater. 2021;132:461–72. https://doi.org/10.1016/j.actbio.2020.12.037
Seino T, Kawasaki S, Shimokawa M, Tamagawa H, Toshimitsu K, Fujii M, et al. Human pancreatic tumor organoids reveal loss of stem cell niche factor dependence during disease progression. Cell Stem Cell. 2018;22(3):454–67.e6. https://doi.org/10.1016/j.stem.2017.12.009
Zhang ZD, Karthaus WR, Lee YS, Gao VR, Wu C, Russo JW, et al. Tumor microenvironment‐derived NRG1 promotes antiandrogen resistance in prostate cancer. Cancer Cell. 2020;38(2):279–96.e9. https://doi.org/10.1016/j.ccell.2020.06.005
Schuth S, le Blanc S, Krieger TG, Jabs J, Schenk M, Giese NA, et al. Patient‐specific modeling of stroma‐mediated chemoresistance of pancreatic cancer using a three‐dimensional organoid‐fibroblast co‐culture system. J Exp Clin Cancer Res. 2022;41(1):312. https://doi.org/10.1186/s13046-022-02519-7
Kuen J, Darowski D, Kluge T, Majety M. Pancreatic cancer cell/fibroblast co‐culture induces M2 like macrophages that influence therapeutic response in a 3D model. PLoS One. 2017;12(7):e0182039. https://doi.org/10.1371/journal.pone.0182039
Cadavid JL, Latour S, Nowlan F, Co IL, Landon‐Brace N, Wouters BG, et al. An engineered paper‐based 3D coculture model of pancreatic cancer to study the impact of tissue architecture and microenvironmental gradients on cell phenotype. Adv Healthcare Mater. 2023;12(14):e2201846. https://doi.org/10.1002/adhm.202201846
DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, et al. CD4+ T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16(2):91–102. https://doi.org/10.1016/j.ccr.2009.06.018
Tsai S, McOlash L, Palen K, Johnson B, Duris C, Yang Q, et al. Development of primary human pancreatic cancer organoids, matched stromal and immune cells and 3D tumor microenvironment models. BMC Cancer. 2018;18(1):335. https://doi.org/10.1186/s12885-018-4238-4
Courau T, Bonnereau J, Chicoteau J, Bottois H, Remark R, Assante Miranda L, et al. Cocultures of human colorectal tumor spheroids with immune cells reveal the therapeutic potential of MICA/B and NKG2A targeting for cancer treatment. J Immunother Cancer. 2019;7(1):74. https://doi.org/10.1186/s40425-019-0553-9
Sebrell TA, Hashimi M, Sidar B, Wilkinson RA, Kirpotina L, Quinn MT, et al. A novel gastric spheroid co‐culture model reveals chemokine‐dependent recruitment of human dendritic cells tothe gastric epithelium. Cell Mol Gastroenterol Hepatol. 2019;8(1):157–71. https://doi.org/10.1016/j.jcmgh.2019.02.010
Holokai L, Chakrabarti J, Broda T, Chang J, Hawkins JA, Sundaram N, et al. Increased programmed death‐ligand 1 is an early epithelial cell response to Helicobacter pylori infection. PLoS Pathog. 2019;15(1):e1007468. https://doi.org/10.1371/journal.ppat.1007468
Silvestri VL, Henriet E, Linville RM, Wong AD, Searson PC, Ewald AJ. A tissue‐engineered 3D microvessel model reveals the dynamics of mosaic vessel formation in breast cancer. Cancer Res. 2020;80(19):4288–301. https://doi.org/10.1158/0008-5472.CAN-19-1564
Lim JTC, Kwang LG, Ho NCW, Toh CCM, Too NSH, Hooi L, et al. Hepatocellular carcinoma organoid co‐cultures mimic angiocrine crosstalk to generate inflammatory tumor microenvironment. Biomaterials. 2022;284:121527. https://doi.org/10.1016/j.biomaterials.2022.121527
Kennedy LB, Salama AKS. A review of cancer immunotherapy toxicity. CA Cancer J Clin. 2020;70(2):86–104. https://doi.org/10.3322/caac.21596
Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov. 2019;18(3):175–96. https://doi.org/10.1038/s41573-018-0006-z
Shen X, Zhao B. Efficacy of PD‐1 or PD‐L1 inhibitors and PD‐L1 expression status in cancer: meta‐analysis. BMJ. 2018;362:k3529. https://doi.org/10.1136/bmj.k3529
Yamamoto TN, Kishton RJ, Restifo NP. Developing neoantigen‐targeted T cell‐based treatments for solid tumors. Nature Med. 2019;25(10):1488–99. https://doi.org/10.1038/s41591-019-0596-y
Sebestyen Z, Prinz I, Déchanet‐Merville J, Silva‐Santos B, Kuball J. Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies. Nat Rev Drug Discov. 2020;19(3):169–84. https://doi.org/10.1038/s41573-019-0038-z
Scognamiglio G, de Chiara A, Parafioriti A, Armiraglio E, Fazioli F, Gallo M, et al. Patient‐derived organoids as a potential model to predict response to PD‐1/PD‐L1 checkpoint inhibitors. Br J Cancer. 2019;121(11):979–82. https://doi.org/10.1038/s41416-019-0616-1
Della Corte CM, Barra G, Ciaramella V, Di Liello R, Vicidomini G, Zappavigna S, et al. Antitumor activity of dual blockade of PD‐L1 and MEK in NSCLC patients derived three‐dimensional spheroid cultures. J Exp Clin Cancer Res. 2019;38(1):253. https://doi.org/10.1186/s13046-019-1257-1
Zhang R, Lin HM, Broering R, Shi XD, Yu XH, Xu LB, et al. Dickkopf‐1 contributes to hepatocellular carcinoma tumorigenesis by activating the Wnt/β‐catenin signaling pathway. Signal Transduct Target Ther. 2019;4:54. https://doi.org/10.1038/s41392-019-0082-5
Sui QQ, Liu DX, Jiang W, Tang JH, Kong LH, Han K, et al. Dickkopf 1 impairs the tumor response to PD‐1 blockade by inactivating CD8+ T cells in deficient mismatch repair colorectal cancer. J Immunother Cancer. 2021;9(3):e001498. https://doi.org/10.1136/jitc-2020-001498
Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer. CA Cancer J Clin. 2021;71(3):264–79. https://doi.org/10.3322/caac.21657
Koikawa K, Kibe S, Suizu F, Sekino N, Kim N, Manz TD, et al. Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy. Cell. 2021;184(18):4753–71.e27. https://doi.org/10.1016/j.cell.2021.07.020
Xiang Z, Zhou ZJ, Song SZ, Li J, Ji J, Yan RL, et al. Dexamethasone suppresses immune evasion by inducing GR/STAT3 mediated downregulation of PD‐L1 and IDO1 pathways. Oncogene. 2021;40(31):5002–12. https://doi.org/10.1038/s41388-021-01897-0
Chakrabarti J, Holokai L, Syu L, Steele N, Chang JL, Dlugosz A, et al. Mouse‐derived gastric organoid and immune cell co‐culture for the study of the tumor microenvironment. Meth Mol Biol Clifton N J. 2018;1817:157–68. https://doi.org/10.1007/978-1-4939-8600-2_16
Braun DA, Wu CJ. Tumor‐infiltrating T cells—a portrait. N Engl J Med. 2022;386(10):992–4. https://doi.org/10.1056/nejmcibr2119477
Yin Q, Yu W, Grzeskowiak CL, Li J, Huang H, Guo J, et al. Nanoparticle‐enabled innate immune stimulation activates endogenous tumor‐infiltrating T cells with broad antigen specificities. Proc Natl Acad Sci. 2021;118(21):e2016168118. https://doi.org/10.1073/pnas.2016168118
Ringquist R, Ghoshal D, Jain R, Roy K. Understanding and improving cellular immunotherapies against cancer: from cell‐manufacturing to tumor‐immune models. Adv Drug Deliv Rev. 2021;179:114003. https://doi.org/10.1016/j.addr.2021.114003
Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020;20(11):651–68. https://doi.org/10.1038/s41577-020-0306-5
Meng Q, Xie S, Gray GK, Dezfulian MH, Gandarilla O, Li W, et al. Empirical identification and validation of tumor‐targeting T cell receptors from circulation using autologous pancreatic tumor organoids. J Immunother Cancer. 2021;9(11):e003213. https://doi.org/10.1136/jitc-2021-003213
Seet CS, He C, Bethune MT, Li S, Chick B, Gschweng EH, et al. Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids. Nat Methods. 2017;14(5):521–30. https://doi.org/10.1038/nmeth.4237
Chung K. Toward off‐the‐shelf adoptive T cell therapies. Sci Transl Med. 2017;9(386):eaan2779. https://doi.org/10.1126/scitranslmed.aan2779
Montel‐Hagen A, Seet CS, Li S, Chick B, Zhu Y, Chang P, et al. Organoid‐induced differentiation of conventional T cells from human pluripotent stem cells. Cell Stem Cell. 2019;24(3):376–89. https://doi.org/10.1016/j.stem.2018.12.011
Wang Z, McWilliams‐Koeppen HP, Reza H, Ostberg JR, Chen W, Wang X, et al. 3D‐organoid culture supports differentiation of human CAR+ iPSCs into highly functional CAR Tcells. Cell Stem Cell. 2022;29(4):651–3. https://doi.org/10.1016/j.stem.2022.02.009
Kaneko S. Successful organoid‐mediated generation of iPSC‐derived CAR‐T cells. Cell Stem Cell. 2022;29(4):493–5. https://doi.org/10.1016/j.stem.2022.03.005
Gan HK, Cvrljevic AN, Johns TG. The epidermal growth factor receptor variant Ⅲ (EGFRvIII): where wild things are altered. FEBS J. 2013;280(21):5350–70. https://doi.org/10.1111/febs.12393
Michie J, Beavis PA, Freeman AJ, Vervoort SJ, Ramsbottom KM, Narasimhan V, et al. Antagonism of IAPs enhances CAR T‐cell efficacy. Cancer Immunol Res. 2019;7(2):183–92. https://doi.org/10.1158/2326-6066.cir-18-0428
Yu L, Li ZC, Mei HB, Li WJ, Chen D, Liu L, et al. Patient‐derived organoids of bladder cancer recapitulate antigen expression profiles and serve as a personal evaluation model for CAR‐T cellsin vitro. Clin Transl Immunol. 2021;10(2):e1248. https://doi.org/10.1002/cti2.1248
Jin WL, Jin MZ, Tu YY. Organoids: a platform ready for glioblastoma precision medicine. Trends Cancer. 2020;6(4):265–7. https://doi.org/10.1016/j.trecan.2020.01.016
Li HX, Harrison EB, Li HZ, Hirabayashi K, Chen J, Li QX, et al. Targeting brain lesions of non‐small cell lung cancer by enhancing CCL2‐mediated CAR‐T cell migration. Nat Commun. 2022;13(1):2154. https://doi.org/10.1038/s41467-022-29647-0
Labrijn AF, Janmaat ML, Reichert JM, Parren PWHI. Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019;18(8):585–608. https://doi.org/10.1038/s41573-019-0028-1
Gonzalez‐Exposito R, Semiannikova M, Griffiths B, Khan K, Barber LJ, Woolston A, et al. CEA expression heterogeneity and plasticity confer resistance to the CEA‐targeting bispecific immunotherapy antibody cibisatamab (CEA‐TCB) in patient‐derived colorectal cancer organoids. J Immunother Cancer. 2019;7(1):101. https://doi.org/10.1186/s40425-019-0575-3
Teijeira A, Migueliz I, Garasa S, Karanikas V, Luri C, Cirella A, et al. Three‐dimensional colon cancer organoids model the response to CEA‐CD3 T‐cell engagers. Theranostics. 2022;12(3):1373–87. https://doi.org/10.7150/thno.63359
Wan C, Keany MP, Dong H, Al‐Alem LF, Pandya UM, Lazo S, et al. Enhanced efficacy of simultaneous PD‐1 and PD‐L1 immune checkpoint blockade in high‐grade serous ovarian cancer. Cancer Res. 2021;81(1):158–73. https://doi.org/10.1158/0008-5472.CAN-20-1674
Ylösmäki E, Cerullo V. Design and application of oncolytic viruses for cancer immunotherapy. Curr Opin Biotechnol. 2020;65:25–36. https://doi.org/10.1016/j.copbio.2019.11.016
Raja J, Ludwig JM, Gettinger SN, Schalper KA, Kim HS. Oncolytic virus immunotherapy: future prospects for oncology. J Immunother Cancer. 2018;6(1):140. https://doi.org/10.1186/s40425-018-0458-z
Wang L, Chard Dunmall LS, Cheng Z, Wang Y. Remodeling the tumor microenvironment by oncolytic viruses: beyond oncolysis of tumor cells for cancer treatment. J Immunother Cancer. 2022;10(5):e004167. https://doi.org/10.1136/jitc-2021-004167
Brown MC, Holl EK, Boczkowski D, Dobrikova E, Mosaheb M, Chandramohan V, et al. Cancer immunotherapy with recombinant poliovirus induces IFN‐dominant activation of dendritic cells and tumor antigen‐specific CTLs. Sci Transl Med. 2017;9(408):eaan4220. https://doi.org/10.1126/scitranslmed.aan4220
Chon HJ, Lee WS, Yang H, Kong SJ, Lee NK, Moon ES, et al. Tumor microenvironment remodeling by intratumoral oncolytic vaccinia virus enhances the efficacy of immune‐checkpoint blockade. Clin Cancer Res. 2019;25(5):1612–23. https://doi.org/10.1158/1078-0432.ccr-18-1932
Raimondi G, Mato‐Berciano A, Pascual‐Sabater S, Rovira‐Rigau M, Cuatrecasas M, Fondevila C, et al. Patient‐derived pancreatic tumour organoids identify therapeutic responses to oncolytic adenoviruses. EBioMedicine. 2020;56:102786. https://doi.org/10.1016/j.ebiom.2020.102786
Zhu Z, Gorman MJ, McKenzie LD, Chai JN, Hubert CG, Prager BC, et al. Zika virus has oncolytic activity against glioblastoma stem cells. J Exp Med. 2017;214(10):2843–57. https://doi.org/10.1084/jem.20171093
Zhu Z, Mesci P, Bernatchez JA, Gimple RC, Wang XX, Schafer ST, et al. Zika virus targets glioblastoma stem cells through a SOX2‐integrin αvβ5 axis. Cell Stem Cell. 2020;26(2):187–204. https://doi.org/10.1016/j.stem.2019.11.016
Hamdan F, Ylösmäki E, Chiaro J, Giannoula Y, Long M, Fusciello M, et al. Novel oncolytic adenovirus expressing enhanced cross‐hybrid IgGA Fc PD‐L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro, in vivo and with patient‐derived tumor organoids. J Immunother Cancer. 2021;9(8):e003000. https://doi.org/10.1136/jitc-2021-003000
Zhang B, Huang J, Tang JL, Hu S, Luo SX, Luo ZG, et al. Intratumoral OH2, an oncolytic herpes simplex virus 2, in patients with advanced solid tumors: a multicenter, phase Ⅰ/Ⅱ clinical trial. J Immunother Cancer. 2021;9(4):e002224. https://doi.org/10.1136/jitc-2020-002224
Goswami S, Basu S, Sharma P. A potential biomarker for anti‐PD‐1 immunotherapy. Nature Med. 2018;24(2):123–4. https://doi.org/10.1038/nm.4489
Chen J, Sun HW, Yang YY, Chen HT, Yu XJ, Wu WC, et al. Reprogramming immunosuppressive myeloid cells by activated T cells promotes the response to anti‐PD‐1 therapy in colorectal cancer. Signal Transduct Target Ther. 2021;6(1):4. https://doi.org/10.1038/s41392-020-00377-3
Holokai L, Chakrabarti J, Lundy J, Croagh D, Adhikary P, Richards SS, et al. Murine‐ and human‐derived autologous organoid/immune cell co‐cultures as pre‐clinical models of pancreatic ductal adenocarcinoma. Cancers. 2020;12(12):3816. https://doi.org/10.3390/cancers12123816
Cho EJ, Kim M, Jo D, Kim J, Oh JH, Chung HC, et al. Immuno‐genomic classification of colorectal cancer organoids reveals cancer cells with intrinsic immunogenic properties associated with patient survival. J Exp Clin Cancer Res. 2021;40(1):230. https://doi.org/10.1186/s13046-021-02034-1
Zou F, Tan JZ, Liu T, Liu BF, Tang YP, Zhang H, et al. The CD39+ HBV surface protein‐targeted CAR‐T and personalized tumor‐reactive CD8+ T cells exhibit potent anti‐HCC activity. Mol Ther. 2021;29(5):1794–807. https://doi.org/10.1016/j.ymthe.2021.01.021
Liu T, Tan JZ, Wu MH, Fan WZ, Wei JL, Zhu BW, et al. High‐affinity neoantigens correlate with better prognosis and trigger potent antihepatocellular carcinoma (HCC) activity by activating CD39+CD8+ T cells. Gut. 2021;70(10):1965–77. https://doi.org/10.1136/gutjnl-2020-322196
Di Nicolantonio F, Vitiello PP, Marsoni S, Siena S, Tabernero J, Trusolino L, et al. Precision oncology in metastatic colorectal cancer—from biology to medicine. Nat Rev Clin Oncol. 2021;18(8):506–25. https://doi.org/10.1038/s41571-021-00495-z
Zhou XW, Qu MY, Tebon P, Jiang X, Wang CR, Xue YM, et al. Screening cancer immunotherapy: when engineering approaches meet artificial intelligence. Adv Sci. 2020;7(19):2001447. https://doi.org/10.1002/advs.202001447
Forsythe SD, Erali RA, Sasikumar S, Laney P, Shelkey E, D'Agostino R, et al. Organoid platform in preclinical investigation of personalized immunotherapy efficacy in appendiceal cancer: feasibility study. Clin Cancer Res. 2021;27(18):5141–50. https://doi.org/10.1158/1078-0432.CCR-21-0982
Cornel AM, Dunnebach E, Hofman DA, Das S, Sengupta S, van den Ham F, et al. Epigenetic modulation of neuroblastoma enhances T cell and NK cell immunogenicity by inducing a tumor‐cell lineage switch. J Immunother Cancer. 2022;10(12):e005002. https://doi.org/10.1136/jitc-2022-005002
Xu HC, van der Jeught K, Zhou ZL, Zhang L, Yu T, Sun YF, et al. Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation. J Clin Invest. 2021;131(10):e146832. https://doi.org/10.1172/jci146832
Dong HJ, Li ZQ, Bian SC, Song GY, Song WF, Zhang MQ, et al. Culture of patient‐derived multicellular clusters in suspended hydrogel capsules for pre‐clinical personalized drug screening. Bioact Mater. 2022;18:164–77. https://doi.org/10.1016/j.bioactmat.2022.03.020
Davidson S, Coles M, Thomas T, Kollias G, Ludewig B, Turley S, et al. Fibroblasts as immune regulators in infection, inflammation and cancer. Nat Rev Immunol. 2021;21(11):704–17. https://doi.org/10.1038/s41577-021-00540-z
Nie YZ, Zheng YW, Miyakawa K, Murata S, Zhang RR, Sekine K, et al. Recapitulation of hepatitis B virus‐host interactions in liver organoids from human induced pluripotent stem cells. EBioMedicine. 2018;35:114–23. https://doi.org/10.1016/j.ebiom.2018.08.014
De Crignis E, Hossain T, Romal S, Carofiglio F, Moulos P, Khalid MM, et al. Application of human liver organoids as a patient‐derived primary model for HBV infection and related hepatocellular carcinoma. eLife. 2021;10:e60747. https://doi.org/10.7554/eLife.60747
Baktash Y, Madhav A, Coller KE, Randall G. Single particle imaging of polarized hepatoma organoids upon hepatitis C virus infection reveals an ordered and sequential entry process. Cell Host Microbe. 2018;23(3):382–94.e5. https://doi.org/10.1016/j.chom.2018.02.005
Pleguezuelos‐Manzano C, Puschhof J, Rosendahl Huber A, van Hoeck A, Wood HM, Nomburg J, et al. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli. Nature. 2020;580(7802):269–73. https://doi.org/10.1038/s41586-020-2080-8
Costa L, Corre S, Michel V, Le Luel K, Fernandes J, Ziveri J, et al. USF1 defect drives p53 degradation during Helicobacter pylori infection and accelerates gastric carcinogenesis. Gut. 2020;69(9):1582–91. https://doi.org/10.1136/gutjnl-2019-318640
Ding L, Chakrabarti J, Sheriff S, Li Q, Thi Hong HN, Sontz RA, et al. Toll‐like receptor 9 pathway mediates schlafen+‐MDSC polarization during Helicobacter‐induced gastric metaplasias. Gastroenterology. 2022;163(2):411–25. https://doi.org/10.1053/j.gastro.2022.04.031
Gao YH, Bi DX, Xie RT, Li M, Guo J, Liu H, et al. Fusobacterium nucleatum enhances the efficacy of PD‐L1 blockade in colorectal cancer. Signal Transduct Target Ther. 2021;6(1):398. https://doi.org/10.1038/s41392-021-00795-x
Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer. 2018;18(7):407–18. https://doi.org/10.1038/s41568-018-0007-6
Magré L, Verstegen MMA, Buschow S, van der Laan LJW, Peppelenbosch M, Desai J. Emerging organoid‐immune co‐culture models for cancer research: from oncoimmunology to personalized immunotherapies. J Immunother Cancer. 2023;11(5):e006290. https://doi.org/10.1136/jitc-2022-006290
Suarez‐Martinez E, Suazo‐Sanchez I, Celis‐Romero M, Carnero A. 3D and organoid culture in research: physiology, hereditary genetic diseases and cancer. Cell Biosci. 2022;12(1):39. https://doi.org/10.1186/s13578-022-00775-w
Kuczek DE, Larsen AMH, Thorseth ML, Carretta M, Kalvisa A, Siersbæk MS, et al. Collagen density regulates the activity of tumor‐infiltrating T cells. J Immunother Cancer. 2019;7(1):68. https://doi.org/10.1186/s40425-019-0556-6
Zhang T, Jia YB, Yu Y, Zhang BJ, Xu F, Guo H. Targeting the tumor biophysical microenvironment to reduce resistance to immunotherapy. Adv Drug Deliv Rev. 2022;186:114319. https://doi.org/10.1016/j.addr.2022.114319
Yuan J, Li XY, Yu SJ. Cancer organoid co‐culture model system: novel approach to guide precision medicine. Front Immunol. 2023;13:1061388. https://doi.org/10.3389/fimmu.2022.1061388
Dong RS, Zhang BX, Zhang XW. Liver organoids: an in vitro 3D model for liver cancer study. Cell Biosci. 2022;12(1):152. https://doi.org/10.1186/s13578-022-00890-8
Rios AC, Clevers H. Imaging organoids: a bright future ahead. Nat Methods. 2018;15(1):24–6. https://doi.org/10.1038/nmeth.4537
Li GL, Ma S, Wu QY, Kong DF, Yang ZR, Gu ZR, et al. Establishment of gastric signet ring cell carcinoma organoid for the therapeutic drug testing. Cell Death Discov. 2022;8(1):6. https://doi.org/10.1038/s41420-021-00803-7
LeSavage BL, Suhar RA, Broguiere N, Lutolf MP, Heilshorn SC. Next‐generation cancer organoids. Nat Mater. 2022;21(2):143–59. https://doi.org/10.1038/s41563-021-01057-5
Guan XY, Huang SG. Advances in the application of 3D tumor models in precision oncology and drug screening. Front Bioeng Biotechnol. 2022;10:1021966. https://doi.org/10.3389/fbioe.2022.1021966
Mu PY, Zhou SJ, Lv T, Xia F, Shen LJ, Wan JF, et al. Newly developed 3D in vitro models to study tumor‐immune interaction. J Exp Clin Cancer Res. 2023;42(1):81. https://doi.org/10.1186/s13046-023-02653-w
Ruiter FAA, Morgan FLC, Roumans N, Schumacher A, Slaats GG, Moroni L, et al. Soft, dynamic hydrogel confinement improves kidney organoid lumen morphology and reduces epithelial–mesenchymal transition in culture. Adv Sci. 2022;9(20):e2200543. https://doi.org/10.1002/advs.202200543
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
