{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T02:24:28Z","timestamp":1786933468863,"version":"build-2736575974"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Microsyst Nanoeng"],"DOI":"10.1038\/s41378-026-01401-2","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T01:45:52Z","timestamp":1786931152000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A tumor-on-a-chip model reveals and targets reciprocal macrophage\u2013NK cell crosstalk to advance immunotherapy screening"],"prefix":"10.1038","volume":"12","author":[{"given":"Xiahe","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiurui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangshuai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huajun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6259-3049","authenticated-orcid":false,"given":"Wu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"1401_CR1","doi-asserted-by":"publisher","first-page":"3335","DOI":"10.1172\/JCI83871","volume":"125","author":"Y Yang","year":"2015","unstructured":"Yang, Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J. Clin. Invest. 125, 3335\u20133337 (2015).","journal-title":"J. Clin. Invest."},{"key":"1401_CR2","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.trecan.2019.05.010","volume":"5","author":"GL Szeto","year":"2019","unstructured":"Szeto, G. L. & Finley, S. D. Integrative approaches to cancer immunotherapy. Trends Cancer 5, 400\u2013410 (2019).","journal-title":"Trends Cancer"},{"key":"1401_CR3","first-page":"86","volume":"70","author":"LB Kennedy","year":"2020","unstructured":"Kennedy, L. B. & Salama, A. K. S. A review of cancer immunotherapy toxicity. CA Cancer J. Clin. 70, 86\u2013104 (2020).","journal-title":"CA Cancer J. Clin."},{"key":"1401_CR4","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1016\/S0140-6736(21)01206-X","volume":"398","author":"MS Carlino","year":"2021","unstructured":"Carlino, M. S., Larkin, J. & Long, G. V. Immune checkpoint inhibitors in melanoma. Lancet 398, 1002\u20131014 (2021).","journal-title":"Lancet"},{"key":"1401_CR5","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/s41586-023-05707-3","volume":"614","author":"L Labanieh","year":"2023","unstructured":"Labanieh, L. & Mackall, C. L. CAR immune cells: design principles, resistance and the next generation. Nature 614, 635\u2013648 (2023).","journal-title":"Nature"},{"key":"1401_CR6","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.1038\/s41590-023-01659-y","volume":"24","author":"OK Dagher","year":"2023","unstructured":"Dagher, O. K. & Posey, A. D. Forks in the road for CAR T and CAR NK cell cancer therapies. Nat. Immunol. 24, 1994\u20132007 (2023).","journal-title":"Nat. Immunol."},{"key":"1401_CR7","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12943-023-01737-7","volume":"22","author":"Y Zhou","year":"2023","unstructured":"Zhou, Y., Cheng, L., Liu, L. & Li, X. NK cells are never alone: crosstalk and communication in tumour microenvironments. Mol. Cancer 22, 34\u201358 (2023).","journal-title":"Mol. Cancer"},{"key":"1401_CR8","doi-asserted-by":"publisher","first-page":"4120","DOI":"10.1073\/pnas.0730640100","volume":"100","author":"R Castriconi","year":"2003","unstructured":"Castriconi, R. et al. Transforming growth factor 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proc. Natl. Acad. Sci. USA 100, 4120\u20134125 (2003).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1401_CR9","doi-asserted-by":"publisher","first-page":"21659","DOI":"10.1073\/pnas.1007654108","volume":"107","author":"F Bellora","year":"2010","unstructured":"Bellora, F. et al. The interaction of human natural killer cells with either unpolarized or polarized macrophages results in different functional outcomes. Proc. Natl. Acad. Sci. USA 107, 21659\u201321664 (2010).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1401_CR10","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1084\/jem.20112738","volume":"209","author":"T O\u2019Sullivan","year":"2012","unstructured":"O\u2019Sullivan, T. et al. Cancer immunoediting by the innate immune system in the absence of adaptive immunity. J. Exp. Med. 209, 1869\u20131882 (2012).","journal-title":"J. Exp. Med."},{"key":"1401_CR11","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/s41590-023-01475-4","volume":"24","author":"MD Park","year":"2023","unstructured":"Park, M. D. et al. TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer. Nat. Immunol. 24, 792\u2013801 (2023).","journal-title":"Nat. Immunol."},{"key":"1401_CR12","doi-asserted-by":"publisher","first-page":"32005","DOI":"10.1073\/pnas.2015343117","volume":"117","author":"S Eisinger","year":"2020","unstructured":"Eisinger, S. et al. Targeting a scavenger receptor on tumor-associated macrophages activates tumor cell killing by natural killer cells. Proc. Natl. Acad. Sci. USA 117, 32005\u201332016 (2020).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1401_CR13","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1152\/physiol.00036.2016","volume":"32","author":"K Duval","year":"2017","unstructured":"Duval, K. et al. Modeling physiological events in 2D vs. 3D cell culture. Physiology 32, 266\u2013277 (2017).","journal-title":"Physiology"},{"key":"1401_CR14","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1038\/s41575-018-0033-6","volume":"15","author":"ZJ Brown","year":"2018","unstructured":"Brown, Z. J., Heinrich, B. & Greten, T. F. Mouse models of hepatocellular carcinoma: an overview and highlights for immunotherapy research. Nat. Rev. Gastroenterol. Hepatol. 15, 536\u2013554 (2018).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"1401_CR15","doi-asserted-by":"publisher","first-page":"4597","DOI":"10.1016\/j.cell.2021.08.005","volume":"184","author":"G Vunjak-Novakovic","year":"2021","unstructured":"Vunjak-Novakovic, G., Ronaldson-Bouchard, K. & Radisic, M. Organs-on-a-chip models for biological research. Cell 184, 4597\u20134611 (2021).","journal-title":"Cell"},{"key":"1401_CR16","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.tibtech.2022.12.018","volume":"41","author":"Y Zhao","year":"2023","unstructured":"Zhao, Y., Wang, E. Y., Lai, F. B. L., Cheung, K. & Radisic, M. Organs-on-a-chip: a union of tissue engineering and microfabrication. Trends Biotechnol. 41, 410\u2013424 (2023).","journal-title":"Trends Biotechnol."},{"key":"1401_CR17","doi-asserted-by":"publisher","first-page":"3884","DOI":"10.1016\/j.celrep.2018.12.015","volume":"25","author":"M Nguyen","year":"2018","unstructured":"Nguyen, M. et al. Dissecting effects of anti-cancer drugs and cancer-associated fibroblasts by on-chip reconstitution of immunocompetent tumor microenvironments. Cell Rep. 25, 3884\u20133893 (2018).","journal-title":"Cell Rep."},{"key":"1401_CR18","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67106","volume":"10","author":"SJ Kerns","year":"2021","unstructured":"Kerns, S. J. et al. Human immunocompetent Organ-on-Chip platforms allow safety profiling of tumor-targeted T-cell bispecific antibodies. eLife 10, e67106 (2021).","journal-title":"eLife"},{"key":"1401_CR19","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1038\/s41467-025-56275-1","volume":"16","author":"A Perucca","year":"2025","unstructured":"Perucca, A. et al. Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing. Nat. Commun. 16, 1279\u20131299 (2025).","journal-title":"Nat. Commun."},{"key":"1401_CR20","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.stem.2024.04.018","volume":"31","author":"TI Maulana","year":"2024","unstructured":"Maulana, T. I. et al. Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells. Cell Stem Cell 31, 989\u20131002 (2024).","journal-title":"Cell Stem Cell"},{"key":"1401_CR21","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc2331","volume":"7","author":"JM Ayuso","year":"2021","unstructured":"Ayuso, J. M. et al. Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion. Sci. Adv. 7, eabc2331 (2021).","journal-title":"Sci. Adv."},{"key":"1401_CR22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2214569119","volume":"119","author":"Z Ao","year":"2022","unstructured":"Ao, Z. et al. Microfluidics guided by deep learning for cancer immunotherapy screening. Proc. Natl. Acad. Sci. USA 119, e2214569119 (2022).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1401_CR23","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13045-024-01549-2","volume":"17","author":"K-Y Shen","year":"2024","unstructured":"Shen, K.-Y., Zhu, Y., Xie, S.-Z. & Qin, L.-X. Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives. J. Hematol. Oncol. 17, 25\u201348 (2024).","journal-title":"J. Hematol. Oncol."},{"key":"1401_CR24","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1038\/s41586-024-08087-4","volume":"634","author":"C-K Mo","year":"2024","unstructured":"Mo, C.-K. et al. Tumour evolution and microenvironment interactions in 2D and 3D space. Nature 634, 1178\u20131186 (2024).","journal-title":"Nature"},{"key":"1401_CR25","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.ccell.2023.01.009","volume":"41","author":"EN Arner","year":"2023","unstructured":"Arner, E. N. & Rathmell, J. C. Metabolic programming and immune suppression in the tumor microenvironment. Cancer Cell 41, 421\u2013433 (2023).","journal-title":"Cancer Cell"},{"key":"1401_CR26","doi-asserted-by":"publisher","first-page":"213421","DOI":"10.1016\/j.bioadv.2023.213421","volume":"149","author":"AP Cameron","year":"2023","unstructured":"Cameron, A. P., Gao, S., Liu, Y. & Zhao, C.-X. Impact of hydrogel biophysical properties on tumor spheroid growth and drug response. Biomater. Adv. 149, 213421\u2013213433 (2023).","journal-title":"Biomater. Adv."},{"key":"1401_CR27","doi-asserted-by":"publisher","first-page":"4855","DOI":"10.1039\/c2lc40306d","volume":"12","author":"K Funamoto","year":"2012","unstructured":"Funamoto, K. et al. A novel microfluidic platform for high-resolution imaging of a three-dimensional cell culture under a controlled hypoxic environment. Lab Chip 12, 4855\u20134863 (2012).","journal-title":"Lab Chip"},{"key":"1401_CR28","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.it.2023.10.007","volume":"44","author":"I Nasir","year":"2023","unstructured":"Nasir, I. et al. Tumor macrophage functional heterogeneity can inform the development of novel cancer therapies. Trends Immunol. 44, 971\u2013985 (2023).","journal-title":"Trends Immunol."},{"key":"1401_CR29","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1038\/s41423-024-01232-z","volume":"21","author":"J Kzhyshkowska","year":"2024","unstructured":"Kzhyshkowska, J., Shen, J. & Larionova, I. Targeting of TAMs: can we be more clever than cancer cells?. Cell. Mol. Immunol. 21, 1376\u20131409 (2024).","journal-title":"Cell. Mol. Immunol."},{"key":"1401_CR30","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adk3981","volume":"9","author":"G Dunsmore","year":"2024","unstructured":"Dunsmore, G. et al. Timing and location dictate monocyte fate and their transition to tumor-associated macrophages. Sci. Immunol. 9, eadk3981 (2024).","journal-title":"Sci. Immunol."},{"key":"1401_CR31","doi-asserted-by":"publisher","first-page":"10232","DOI":"10.1038\/s41467-024-54145-w","volume":"15","author":"X Wang","year":"2024","unstructured":"Wang, X. et al. Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications. Nat. Commun. 15, 10232\u201310254 (2024).","journal-title":"Nat. Commun."},{"key":"1401_CR32","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1002\/cac2.12345","volume":"42","author":"K Cheng","year":"2022","unstructured":"Cheng, K. et al. Tumor-associated macrophages in liver cancer: From mechanisms to therapy. Cancer Commun. 42, 1112\u20131140 (2022).","journal-title":"Cancer Commun."},{"key":"1401_CR33","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13045-023-01498-2","volume":"16","author":"HR Jin","year":"2023","unstructured":"Jin, H. R. et al. Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics. J. Hematol. Oncol. 16, 103 (2023).","journal-title":"J. Hematol. Oncol."},{"key":"1401_CR34","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.tibtech.2023.10.001","volume":"42","author":"M Jouybar","year":"2024","unstructured":"Jouybar, M. et al. Cancer-on-chip models for metastasis: importance of the tumor microenvironment. Trends Biotechnol. 42, 431\u2013448 (2024).","journal-title":"Trends Biotechnol."},{"key":"1401_CR35","doi-asserted-by":"publisher","first-page":"114365","DOI":"10.1016\/j.addr.2022.114365","volume":"187","author":"J Zhang","year":"2022","unstructured":"Zhang, J. et al. Immunotherapy discovery on tumor organoid-on-a-chip platforms that recapitulate the tumor microenvironment. Adv. Drug Del. Rev. 187, 114365\u2013114390 (2022).","journal-title":"Adv. Drug Del. Rev."},{"key":"1401_CR36","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1038\/s41551-018-0236-8","volume":"2","author":"CB Rodell","year":"2018","unstructured":"Rodell, C. B. et al. TLR7\/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy. Nat. Biomed. Eng. 2, 578\u2013588 (2018).","journal-title":"Nat. Biomed. Eng."},{"key":"1401_CR37","doi-asserted-by":"publisher","first-page":"81","DOI":"10.3892\/ijo.2022.5371","volume":"61","author":"J Zhou","year":"2022","unstructured":"Zhou, J. et al. The TLR7\/8 agonist R848 optimizes host and tumor immunity to improve therapeutic efficacy in murine lung cancer. Int. J. Oncol. 61, 81\u201392 (2022).","journal-title":"Int. J. Oncol."},{"key":"1401_CR38","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1038\/ni758","volume":"3","author":"H Hemmi","year":"2002","unstructured":"Hemmi, H. et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88\u2013dependent signaling pathway. Nat. Immunol. 3, 196\u2013200 (2002).","journal-title":"Nat. Immunol."},{"key":"1401_CR39","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s41590-018-0132-0","volume":"19","author":"Q Zhang","year":"2018","unstructured":"Zhang, Q. et al. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nat. Immunol. 19, 723\u2013732 (2018).","journal-title":"Nat. Immunol."},{"key":"1401_CR40","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s40364-023-00543-z","volume":"12","author":"P Zhang","year":"2024","unstructured":"Zhang, P. et al. Targeting TIGIT for cancer immunotherapy: recent advances and future directions. Biomark. Res. 12, 7\u201330 (2024).","journal-title":"Biomark. Res."},{"key":"1401_CR41","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1007\/s00262-025-04128-7","volume":"74","author":"EC Sundstrom","year":"2025","unstructured":"Sundstrom, E. C., Huang, X. & Wiemer, A. J. Anti-TIGIT therapies: a review of preclinical and clinical efficacy and mechanisms. Cancer Immunol., Immunother. 74, 272\u2013286 (2025).","journal-title":"Cancer Immunol., Immunother."},{"key":"1401_CR42","doi-asserted-by":"publisher","first-page":"5819","DOI":"10.1038\/s41467-025-60757-7","volume":"16","author":"D Hsiehchen","year":"2025","unstructured":"Hsiehchen, D. et al. Dual TIGIT and PD-1 blockade with domvanalimab plus zimberelimab in hepatocellular carcinoma refractory to anti-PD-1 therapies: the phase 2 LIVERTI trial. Nat. Commun. 16, 5819\u20135826 (2025).","journal-title":"Nat. Commun."},{"key":"1401_CR43","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.1182\/blood-2010-02-271874","volume":"116","author":"DM Benson","year":"2010","unstructured":"Benson, D. M. et al. The PD-1\/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti\u2013PD-1 antibody. Blood 116, 2286\u20132294 (2010).","journal-title":"Blood"},{"key":"1401_CR44","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1158\/2326-6066.CIR-17-0035","volume":"6","author":"C Li","year":"2018","unstructured":"Li, C. et al. Peptide blocking of PD-1\/PD-L1 interaction for cancer immunotherapy. Cancer Immunol. Res. 6, 178\u2013188 (2018).","journal-title":"Cancer Immunol. Res."},{"key":"1401_CR45","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41577-023-00973-8","volume":"24","author":"LH Butterfield","year":"2023","unstructured":"Butterfield, L. H. & Najjar, Y. G. Immunotherapy combination approaches: mechanisms, biomarkers and clinical observations. Nat. Rev. Immunol. 24, 399\u2013416 (2023).","journal-title":"Nat. Rev. Immunol."},{"key":"1401_CR46","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70346","volume":"6","author":"X Wang","year":"2025","unstructured":"Wang, X. & Jing, J. Cancer immunotherapy in combination with radiotherapy and\/or chemotherapy: mechanisms and clinical therapy. MedComm 6, e70346 (2025).","journal-title":"MedComm"},{"key":"1401_CR47","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41568-018-0095-3","volume":"19","author":"U Ben-David","year":"2019","unstructured":"Ben-David, U., Beroukhim, R. & Golub, T. R. Genomic evolution of cancer models: perils and opportunities. Nat. Rev. Cancer 19, 97\u2013109 (2019).","journal-title":"Nat. Rev. Cancer"},{"key":"1401_CR48","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/nbt1186","volume":"24","author":"N Malo","year":"2006","unstructured":"Malo, N., Hanley, J. A., Cerquozzi, S., Pelletier, J. & Nadon, R. Statistical practice in high-throughput screening data analysis. Nat. Biotechnol. 24, 167\u2013175 (2006).","journal-title":"Nat. Biotechnol."},{"key":"1401_CR49","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/s40425-019-0724-8","volume":"7","author":"SR Mullins","year":"2019","unstructured":"Mullins, S. R. et al. Intratumoral immunotherapy with TLR7\/8 agonist MEDI9197 modulates the tumor microenvironment leading to enhanced activity when combined with other immunotherapies. J. ImmunoTher. Cancer 7, 244 (2019).","journal-title":"J. ImmunoTher. Cancer"},{"key":"1401_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-023-00364-1","volume":"7","author":"C Rolfo","year":"2023","unstructured":"Rolfo, C., Giovannetti, E., Martinez, P., McCue, S. & Naing, A. Applications and clinical trial landscape using Toll-like receptor agonists to reduce the toll of cancer. npj Precis. Oncol. 7, 26 (2023).","journal-title":"npj Precis. Oncol."},{"key":"1401_CR51","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.4049\/jimmunol.1700737","volume":"200","author":"SY Nu\u00f1ez","year":"2018","unstructured":"Nu\u00f1ez, S. Y. et al. Human M2 macrophages limit NK cell effector functions through secretion of TGF-\u03b2 and engagement of CD85j. J. Immunol. 200, 1008\u20131015 (2018).","journal-title":"J. Immunol."},{"key":"1401_CR52","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1038\/ni.3800","volume":"18","author":"Y Gao","year":"2017","unstructured":"Gao, Y. et al. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nat. Immunol. 18, 1004\u20131015 (2017).","journal-title":"Nat. Immunol."},{"key":"1401_CR53","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1016\/j.cell.2018.11.021","volume":"175","author":"JT Neal","year":"2018","unstructured":"Neal, J. T. et al. Organoid modeling of the tumor immune microenvironment. Cell 175, 1972\u20131988 (2018).","journal-title":"Cell"},{"key":"1401_CR54","doi-asserted-by":"publisher","first-page":"3149","DOI":"10.1158\/0008-5472.CAN-20-4026","volume":"81","author":"M Gronholm","year":"2021","unstructured":"Gronholm, M. et al. Patient-derived organoids for precision cancer immunotherapy. Cancer Res 81, 3149\u20133155 (2021).","journal-title":"Cancer Res"},{"key":"1401_CR55","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-024-03628-3","volume":"24","author":"P Li","year":"2024","unstructured":"Li, P., Huang, M., Ma, Y., Zhang, Y. & Shi, C. Novel research model for in vitro immunotherapy: co-culturing tumor organoids with peripheral blood mononuclear cells. Cancer Cell Int 24, 438 (2024).","journal-title":"Cancer Cell Int"},{"key":"1401_CR56","doi-asserted-by":"crossref","unstructured":"Li, K. et al. An organoid co-culture model for probing systemic anti-tumor immunity in lung cancer. Cell Stem Cell 32, 1218\u20131234 (2025).","DOI":"10.1016\/j.stem.2025.05.011"},{"key":"1401_CR57","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adi2952","volume":"16","author":"SY Neo","year":"2024","unstructured":"Neo, S. Y. et al. Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6\/STAT3 axis. Sci. Transl. Med. 16, eadi2952 (2024).","journal-title":"Sci. Transl. Med."},{"key":"1401_CR58","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.323","volume":"4","author":"R Ren","year":"2023","unstructured":"Ren, R. et al. The recent progress of myeloid-derived suppressor cell and its targeted therapies in cancers. MedComm 4, e323 (2023).","journal-title":"MedComm"},{"key":"1401_CR59","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.ccell.2014.10.018","volume":"26","author":"RobertJ Johnston","year":"2014","unstructured":"Johnston, R. obertJ. et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8 + T cell effector function. Cancer Cell 26, 923\u2013937 (2014).","journal-title":"Cancer Cell"},{"key":"1401_CR60","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.immuni.2022.02.005","volume":"55","author":"KL Banta","year":"2022","unstructured":"Banta, K. L. et al. Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8+ T cell responses. Immunity 55, 512\u2013526 (2022).","journal-title":"Immunity"},{"key":"1401_CR61","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1038\/s41586-024-07121-9","volume":"627","author":"X Guan","year":"2024","unstructured":"Guan, X. et al. Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells. Nature 627, 646\u2013655 (2024).","journal-title":"Nature"},{"key":"1401_CR62","doi-asserted-by":"publisher","first-page":"1335836","DOI":"10.3389\/fphar.2024.1335836","volume":"15","author":"Q Deng","year":"2024","unstructured":"Deng, Q. et al. Assessing immune hepatotoxicity of troglitazone with a versatile liver-immune-microphysiological-system. Front. Pharmacol. 15, 1335836 (2024).","journal-title":"Front. Pharmacol."},{"key":"1401_CR63","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/nrc3186","volume":"12","author":"MA Swartz","year":"2012","unstructured":"Swartz, M. A. & Lund, A. W. Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity. Nat. Rev. Cancer 12, 210\u2013219 (2012).","journal-title":"Nat. Rev. Cancer"}],"container-title":["Microsystems & Nanoengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41378-026-01401-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41378-026-01401-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41378-026-01401-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T01:45:54Z","timestamp":1786931154000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41378-026-01401-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1401"],"URL":"https:\/\/doi.org\/10.1038\/s41378-026-01401-2","relation":{},"ISSN":["2055-7434"],"issn-type":[{"value":"2055-7434","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"assertion":[{"value":"12 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 June 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Ethical approval was obtained from the Institutional Review Board of Shandong University (approval number: KYLL-2024-308).","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"295"}}