Vitale I, Shema E, Loi S, Galluzzi L (2021) Intratumoral heterogeneity in cancer progression and response to immunotherapy. Nat Med 27:212–224. https://doi.org/10.1038/s41591-021-01233-9

Chappell L, Russell AJC, Voet T (2018) Single-cell (multi)omics technologies. Annu Rev Genom Hum Genet 19:15–41. https://doi.org/10.1146/annurev-genom-091416-035324

Article  CAS  Google Scholar 

Goltsev Y, Samusik N, Kennedy-Darling J et al (2018) Deep profiling of mouse splenic architecture with CODEX multiplexed imaging. Cell 174:968-981.e15. https://doi.org/10.1016/j.cell.2018.07.010

Article  CAS  Google Scholar 

Kinkhabwala A, Herbel C, Pankratz J et al (2022) MACSima imaging cyclic staining (MICS) technology reveals combinatorial target pairs for CAR T cell treatment of solid tumors. Sci Rep 12:1911. https://doi.org/10.1038/s41598-022-05841-4

Article  CAS  Google Scholar 

Angelo M, Bendall SC, Finck R et al (2014) Multiplexed ion beam imaging of human breast tumors. Nat Med 20:436–442. https://doi.org/10.1038/nm.3488

Article  CAS  Google Scholar 

Giesen C, Wang HAO, Schapiro D et al (2014) Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat Methods 11:417–422. https://doi.org/10.1038/nmeth.2869

Article  CAS  Google Scholar 

Han G, Spitzer MH, Bendall SC et al (2018) Metal-isotope-tagged monoclonal antibodies for high-dimensional mass cytometry. Nat Protoc 13:2121–2148. https://doi.org/10.1038/s41596-018-0016-7

Article  CAS  Google Scholar 

Allo B, Lou X, Bouzekri A, Ornatsky O (2018) Clickable and high-sensitivity metal-containing tags for mass cytometry. Bioconjugate Chem 29:2028–2038. https://doi.org/10.1021/acs.bioconjchem.8b00239

Article  CAS  Google Scholar 

Rovira-Clavé X, Jiang S, Bai Y et al (2021) Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging. Nat Commun 12:4628. https://doi.org/10.1038/s41467-021-24822-1

Article  CAS  Google Scholar 

Chang Q, Ornatsky OI, Siddiqui I et al (2016) Biodistribution of cisplatin revealed by imaging mass cytometry identifies extensive collagen binding in tumor and normal tissues. Sci Rep 6:36641. https://doi.org/10.1038/srep36641

Article  CAS  Google Scholar 

Catena R, Montuenga LM, Bodenmiller B (2018) Ruthenium counterstaining for imaging mass cytometry: ruthenium-based metal counterstaining for imaging mass cytometry. J Pathol 244:479–484. https://doi.org/10.1002/path.5049

Article  CAS  Google Scholar 

Ijsselsteijn ME, van der Breggen R, Farina Sarasqueta A et al (2019) A 40-marker panel for high dimensional characterization of cancer immune microenvironments by imaging mass cytometry. Front Immunol 10:2534. https://doi.org/10.3389/fimmu.2019.02534

Article  CAS  Google Scholar 

Gheiratmand L, Brown DJ, Sandkuijl D et al (2022) Immuno tomography (IT) and imaging mass cytometry (IMC) for constructing spatially resolved, multiplexed 3D IMC data sets. Ocul Surf 25:49–54. https://doi.org/10.1016/j.jtos.2022.04.008

Article  Google Scholar 

Chang Q, Ornatsky O, Hedley D (2017) Staining of frozen and formalin‐fixed, paraffin‐embedded tissues with metal‐labeled antibodies for imaging mass cytometry analysis. CurrProtoc Cytom 82. https://doi.org/10.1002/cpcy.29

Elaldi R, Hemon P, Petti L et al (2021) High dimensional imaging mass cytometry panel to visualize the tumor immune microenvironment contexture. Front Immunol 12:666233. https://doi.org/10.3389/fimmu.2021.666233

Article  CAS  Google Scholar 

Schulz D, Zanotelli VRT, Fischer JR et al (2018) Simultaneous multiplexed imaging of mRNA and proteins with subcellular resolution in breast cancer tissue samples by mass cytometry. Cell Syst 6:25-36.e5. https://doi.org/10.1016/j.cels.2017.12.001

Article  CAS  Google Scholar 

Keren L, Bosse M, Thompson S et al (2019) MIBI-TOF: a multiplexed imaging platform relates cellular phenotypes and tissue structure. Sci Adv 5:eaax5851. https://doi.org/10.1126/sciadv.aax5851

Article  CAS  Google Scholar 

Keren L, Bosse M, Marquez D et al (2018) A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging. Cell 174:1373-1387.e19. https://doi.org/10.1016/j.cell.2018.08.039

Article  CAS  Google Scholar 

Zanotelli VRT, Bodenmiller B (2017) ImcSegmentationPipeline: a pixelclassification based multiplexed image segmentation pipeline

Berg S, Kutra D, Kroeger T et al (2019) ilastik: interactive machine learning for (bio)image analysis. Nat Methods 16:1226–1232. https://doi.org/10.1038/s41592-019-0582-9

Article  CAS  Google Scholar 

Stirling DR, Swain-Bowden MJ, Lucas AM et al (2021) Cell Profiler 4: improvements in speed, utility and usability. BMC Bioinformatics 22:433. https://doi.org/10.1186/s12859-021-04344-9

Article  Google Scholar 

Kotecha N, Krutzik PO, Irish JM (2010) Web-based analysis and publication of flow cytometry experiments. Curr Protoc Cytom Chapter 10:Unit10.17. https://doi.org/10.1002/0471142956.cy1017s53

Article  Google Scholar 

Ijsselsteijn ME, Somarakis A, Lelieveldt BPF et al (2021) Semi-automated background removal limits data loss and normalizes imaging mass cytometry data. Cytometry Pt A 99:1187–1197. https://doi.org/10.1002/cyto.a.24480

Article  CAS  Google Scholar 

Chevrier S, Crowell HL, Zanotelli VRT et al (2018) Compensation of signal spillover in suspension and imaging mass cytometry. Cell Syst 6:612-620.e5. https://doi.org/10.1016/j.cels.2018.02.010

Article  CAS  Google Scholar 

Greenwald NF, Miller G, Moen E et al (2022) Whole-cell segmentation of tissue images with human-level performance using large-scale data annotation and deep learning. Nat Biotechnol 40:555–565. https://doi.org/10.1038/s41587-021-01094-0

Article  CAS  Google Scholar 

Bai Y, Zhu B, Rovira-Clave X et al (2021) Adjacent cell marker lateral spillover compensation and reinforcement for multiplexed images. Front Immunol 12:652631. https://doi.org/10.3389/fimmu.2021.652631

Article  CAS  Google Scholar 

Allam M, Hu T, Lee J et al (2022) Spatially variant immune infiltration scoring in human cancer tissues. npj Precis Onc 6:60. https://doi.org/10.1038/s41698-022-00305-4

Article  CAS  Google Scholar 

McInnes L, Healy J, Melville J (2020) UMAP: Uniform manifold approximation and projection for dimension reduction. arXiv:1802.03426. https://doi.org/10.48550/arXiv.1802.03426

van der Maaten L, Hinton GE (2008) Visualizing data using t-SNE. J Mach Learn Res 9:2579–2605

Google Scholar 

Bruggner RV, Bodenmiller B, Dill DL, et al (2014) Automated identification of stratifying signatures in cellular subpopulations. Proc Natl Acad Sci USA 111. https://doi.org/10.1073/pnas.1408792111

Jackson HW, Fischer JR, Zanotelli VRT et al (2020) The single-cell pathology landscape of breast cancer. Nature 578:615–620. https://doi.org/10.1038/s41586-019-1876-x

Article  CAS  Google Scholar 

Schapiro D, Jackson HW, Raghuraman S et al (2017) histoCAT: analysis of cell phenotypes and interactions in multiplex image cytometry data. Nat Methods 14:873–876. https://doi.org/10.1038/nmeth.4391

Article  CAS  Google Scholar 

Somarakis A, Van Unen V, Koning F et al (2021) ImaCytE: visual exploration of cellular micro-environments for imaging mass cytometry data. IEEE Trans Visual Comput Graphics 27:98–110. https://doi.org/10.1109/TVCG.2019.2931299

Article  Google Scholar 

Kuett L, Catena R, Özcan A, Plüss A, Cancer Grand Challenges IMAXT Consortium, Schraml P, Moch H, de Souza N, Bodenmiller B (2022) Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment. Nat Cancer 3:122–133. https://doi.org/10.1038/s43018-021-00301-w

Melin N, Yarahmadov T, Sanchez-Taltavull D et al (2022) A new mouse model of radiation-induced liver disease reveals mitochondrial dysfunction as an underlying fibrotic stimulus. JHEP Reports 4:100508. https://doi.org/10.1016/j.jhepr.2022.100508

Article  Google Scholar 

Zabransky DJ, Danilova L, Leatherman JM, et al (2022) Profiling of murine syngeneic HCC tumor models as a framework to understand anti-PD-1 sensitive tumor microenvironments. Hepatology hep.32707. https://doi.org/10.1002/hep.32707

Peran I, Dakshanamurthy S, McCoy MD et al (2021) Cadherin 11 promotes immunosuppression and extracellular matrix deposition to support growth of pancreatic tumors and resistance to gemcitabine in mice. Gastroenterology 160:1359-1372.e13. https://doi.org/10.1053/j.gastro.2020.11.044

Article  CAS  Google Scholar 

van Maldegem F, Valand K, Cole M et al (2021) Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry. Nat Commun 12:5906. https://doi.org/10.1038/s41467-021-26214-x

Article  CAS  Google Scholar 

Liu H-C, Viswanath DI, Pesaresi F et al (2021) Potentiating antitumor efficacy through radiation and sustained intratumoral delivery of anti-CD40 and anti-PDL1. Int J Radiat Oncol*Biol*Phys 110:492–506. https://doi.org/10.1016/j.ijrobp.2020.07.2326

Article  Google Scholar 

Strittmatter N, Moss JI, Race AM et al (2022) Multi-modal molecular imaging maps the correlation between tumor microenvironments and nanomedicine distribution. Theranostics 12:2162–2174. https://doi.org/10.7150/thno.68000

Article  CAS  Google Scholar 

Strittmatter N, Richards FM, Race AM et al (2022) Method to visualize the intratumor distribution and impact of gemcitabine in pancreatic ductal adenocarcinoma by multimodal imaging. Anal Chem 94:1795–1803. https://doi.org/10.1021/acs.analchem.1c04579

Article  CAS  Google Scholar 

Lotsberg ML, Røsland GV, Rayford AJ et al (2022) Intrinsic differences in spatiotemporal organization and stromal cell interactions between isogenic lung cancer cells of epithelial and mesenchymal phenotypes revealed by high-dimensional single-cell analysis of heterotypic 3D spheroid models. Front Oncol 12:818437. https://doi.org/10.3389/fonc.2022.818437

Article  Google Scholar 

Guo N, Jia L, Out-Luiting C et al (2022) Mass cytometric analysis of early-stage mycosis fungoides. Cells 11:1062. https://doi.org/10.3390/cells11071062

Article  CAS  Google Scholar 

Wang AZ, Bowman-Kirigin JA, Desai R et al (2022) Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response. Genome Med 14:49. https://doi.org/10.1186/s13073-022-01051-9

Article  CAS  Google Scholar 

Sanmamed MF, Nie X, Desai SS et al (2021) A burned-out CD8+ T-cell subset expands in the tumor microenvironment and curbs cancer immunotherapy. Cancer Discov 11:1700–1715. https://doi.org/10.1158/2159-8290.CD-20-0962

Article  CAS  Google Scholar 

Sheng J, Zhang J, Wang L et al (2022) Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals cellular neighbourhood regulated reversely by macrophages with different ontogeny. Gut 71:1176–1191. https://doi.org/10.1136/gutjnl-2021-324339

Article  CAS  Google Scholar 

Ferrian S, Liu CC, McCaffrey EF et al (2021) Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis. Cell Reports Medicine 2:100419. https://doi.org/10.1016/j.xcrm.2021.100419

Article  CAS  Google Scholar 

Zheng Y, Han L, Chen Z et al (2022) PD-L1+CD8+ T cells enrichment in lung cancer exerted regulatory function and tumor-promoting tolerance. iScience 25:103785. https://doi.org/10.1016/j.isci.2022.103785

Article