Skip to main content

Advertisement

SpringerLink
Log in

Neue Methoden der multiparametrischen Gewebediagnostik

Novel methods of multiparametric tissue diagnostics

  • Leitthema
  • Published:
Die Onkologie Aims and scope

Zusammenfassung

In den letzten Jahren wurden verschiedene Methoden der multiparametrischen Gewebediagnostik entwickelt, die eine detaillierte molekulare, zelluläre und architektonische Charakterisierung des Mikromilieus solider Tumoren ermöglichen. Fluoreszenzbasierte Methoden wie die Tyramid-Signalamplifikation sowie neuartige massenspektrometrische Verfahren wie die bildgebende Massenzytometrie erlauben die gleichzeitige Analyse einer großen Anzahl von Proteinmarkern in einem Gewebeschnitt. Zyklische Immunfärbungen und DNA-Barcoding-Ansätze können theoretisch sogar unbeschränkt viele Targets analysieren. Die Methoden liefern faszinierende Einblicke in die Komplexität der Tumorbiologie, bringen aber auch Herausforderungen hinsichtlich der Probennahme, Datenanalyse und klinischen Validierung mit sich.

Abstract

In recent years, various methods of multiparametric tissue diagnostics have been developed that allow a detailed molecular, cellular, and architectural characterization of the microenvironment of solid tumors. Fluorescence-based methods such as tyramide signal amplification as well as novel mass spectrometric techniques like imaging mass cytometry enable the simultaneous analysis of a large number of protein markers in a tissue section. Cyclic immunostaining and DNA barcoding approaches can theoretically even analyze unlimited targets. These methods provide fascinating insights into the complexity of tumor biology but also raise challenges regarding sampling, data analysis and clinical validation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. van der Loos CM (2008) Multiple immunoenzyme staining: methods and visualizations for the observation with spectral imaging. J Histochem Cytochem 56(4):313–328. https://doi.org/10.1369/jhc.2007.950170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Glass G, Papin JA, Mandell JW (2009) Simple: a sequential Immunoperoxidase labeling and erasing method. J Histochem Cytochem 57(10):899–905. https://doi.org/10.1369/jhc.2009.953612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Akturk G, Sweeney R, Remark R, Merad M, Gnjatic S (2020) Multiplexed Immunohistochemical consecutive staining on single slide (MICSSS): multiplexed chromogenic IHC assay for high-dimensional tissue analysis. In: Thurin M, Cesano A, Marincola FM (Hrsg) Biomarkers for immunotherapy of cancer: methods and protocols. Methods in molecular biology. Springer, S 497–519 https://doi.org/10.1007/978-1-4939-9773-2_23

    Chapter  Google Scholar 

  4. Weigert M, Schmidt U, Haase R, Sugawara K, Myers G (2020) Star-convex polyhedra for 3D object detection and segmentation in microscopy. In: IEEE winter conference on applications of computer vision (WACV). IEEE, S 3655–3662 https://doi.org/10.1109/WACV45572.2020.9093435 (2020)

    Chapter  Google Scholar 

  5. 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(4):555–565. https://doi.org/10.1038/s41587-021-01094-0

    Article  CAS  PubMed  Google Scholar 

  6. Stringer C, Wang T, Michaelos M, Pachitariu M (2021) Cellpose: a generalist algorithm for cellular segmentation. Nat Methods 18(1):100–106. https://doi.org/10.1038/s41592-020-01018-x

    Article  CAS  PubMed  Google Scholar 

  7. Potts SJ, Johnson TD, Voelker FA, Lange H, Young GD (2011) Multiplexed measurement of proteins in tissue in a clinical environment. Appl Immunohistochem Mol Morphol 19(6):494–498. https://doi.org/10.1097/PAI.0b013e318229ea9e

    Article  CAS  PubMed  Google Scholar 

  8. Mayer A, Schneider F, Vaupel P, Sommer C, Schmidberger H (2012) Differential expression of HIF‑1 in glioblastoma multiforme and anaplastic astrocytoma. Int J Oncol 41(4):1260–1270. https://doi.org/10.3892/ijo.2012.1555

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kijani S, Yrlid U, Heyden M, Levin M, Borén J, Fogelstrand P (2015) Filter-dense multicolor microscopy. PLoS One 10(3):e119499. https://doi.org/10.1371/journal.pone.0119499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Reitz SJ, Sauerbeck AD, Kummer TT (2021) Enhanced multiplexing of Immunofluorescence microscopy using a long-stokes-shift fluorophore. Curr Protoc 1(8):e214. https://doi.org/10.1002/cpz1.214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tóth ZE, Mezey E (2007) Simultaneous visualization of multiple antigens with tyramide signal amplification using antibodies from the same species. J Histochem Cytochem 55(6):545–554. https://doi.org/10.1369/jhc.6A7134.2007

    Article  CAS  PubMed  Google Scholar 

  12. Haist M, Kaufmann J, Kur IM et al (2023) Response to primary chemoradiotherapy of locally advanced oropharyngeal carcinoma is determined by the degree of cytotoxic T cell infiltration within tumor cell aggregates. Front Immunol. https://doi.org/10.3389/fimmu.2023.1070203 (Accessed July 8, 2023)

    Article  PubMed  PubMed Central  Google Scholar 

  13. Gerdes M, Sevinsky CJ, Sood A et al (2013) Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue. Proc Natl Acad Sci USA 110:11982–11987. https://doi.org/10.1073/pnas.1300136110

    Article  PubMed  PubMed Central  Google Scholar 

  14. 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(1):1911. https://doi.org/10.1038/s41598-022-05841-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Goltsev Y, Samusik N, Kennedy-Darling J et al (2017) 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 

  16. Black S, Phillips D, Hickey JW et al (2021) CODEX multiplexed tissue imaging with DNA-conjugated antibodies. Nat Protoc 16(8):3802–3835. https://doi.org/10.1038/s41596-021-00556-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schürch CM, Bhate SS, Barlow GL et al (2020) Coordinated cellular neighborhoods orchestrate antitumoral immunity at the colorectal cancer invasive front. Cell 182(5):1341–1359.e19. https://doi.org/10.1016/j.cell.2020.07.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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  PubMed  Google Scholar 

  19. Qiu P, Simonds EF, Bendall SC et al (2011) Extracting a cellular hierarchy from high-dimensional cytometry data with SPADE. Nat Biotechnol 29(10):886–891. https://doi.org/10.1038/nbt.1991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ali H, Jackson H, Zanotelli VRT et al (2020) Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer. Nat Cancer 1:163–175. https://doi.org/10.1038/s43018-020-0026-6

    Article  CAS  PubMed  Google Scholar 

  21. Kuett L, Catena R, Özcan A et al (2022) Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment. Nat Cancer 3(1):122–133. https://doi.org/10.1038/s43018-021-00301-w

    Article  CAS  PubMed  Google Scholar 

  22. Angelo M, Bendall SC, Finck R et al (2014) Multiplexed ion beam imaging of human breast tumors. Nat Med 20(4):436–442. https://doi.org/10.1038/nm.3488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 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(6):1373–1387.e19. https://doi.org/10.1016/j.cell.2018.08.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ji AL, Rubin AJ, Thrane K et al (2020) Multimodal analysis of composition and spatial architecture in human squamous cell carcinoma. Cell 182(2):497–514.e22. https://doi.org/10.1016/j.cell.2020.05.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Risom T, Glass DR, Averbukh I et al (2022) Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma. Cell 185(2):299–310.e18. https://doi.org/10.1016/j.cell.2021.12.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jackson H, 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  PubMed  Google Scholar 

  27. Saka SK, Wang Y, Kishi JY et al (2019) Immuno-SABER enables highly multiplexed and amplified protein imaging in tissues. Nat Biotechnol 37:1080–1090. https://doi.org/10.1038/s41587-019-0207-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hickey JW, Tan Y, Nolan GP, Goltsev Y (2021) Strategies for accurate cell type identification in CODEX multiplexed imaging data. Front Immunol 12:727626. https://doi.org/10.3389/fimmu.2021.727626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Brbić M, Cao K, Hickey JW et al (2022) Annotation of spatially resolved single-cell data with STELLAR. Nat Methods 19(11):1411–1418. https://doi.org/10.1038/s41592-022-01651-8

    Article  CAS  PubMed  Google Scholar 

  30. Kaufmann J, Biscio CAN, Bankhead P et al (2021) Using the R package spatstat to assess inhibitory effects of microregional hypoxia on the infiltration of cancers of the head and neck region by cytotoxic T lymphocytes. Cancers (Basel) 13(8):1924. https://doi.org/10.3390/cancers13081924

    Article  CAS  PubMed  Google Scholar 

  31. Vu T, Wrobel J, Bitler BG, Schenk EL, Jordan KR, Ghosh D (2022) SPF: a spatial and functional data analytic approach to cell imaging data. Meier-schellersheim M, ed. PLoS Comput Biol 18(6):e1009486. https://doi.org/10.1371/journal.pcbi.1009486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Elhanani O, Ben-Uri R, Keren L (2023) Spatial profiling technologies illuminate the tumor microenvironment. Cancer Cell 41(3):404–420. https://doi.org/10.1016/j.ccell.2023.01.010

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik und Poliklinik für Radioonkologie und Strahlentherapie, Universitätsmedizin Mainz, Mainz, Deutschland

    Arnulf Mayer

  2. Head and Neck Radiation Oncology Unit, Peter MacCallum Cancer Centre, 305 Grattan Street, 3000, Melbourne, Victoria, Australien

    Arnulf Mayer

  3. Hautklinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland

    Maximilian Haist

  4. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

    Maximilian Haist

  5. Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA

    Maximilian Haist

Authors
  1. Arnulf Mayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maximilian Haist
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arnulf Mayer.

Ethics declarations

Interessenkonflikt

A. Mayer und M. Haist geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

Hinweis des Verlags

Der Verlag bleibt in Hinblick auf geografische Zuordnungen und Gebietsbezeichnungen in veröffentlichten Karten und Institutsadressen neutral.

figure qr

QR-Code scannen & Beitrag online lesen

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mayer, A., Haist, M. Neue Methoden der multiparametrischen Gewebediagnostik. Onkologie 29, 1069–1077 (2023). https://doi.org/10.1007/s00761-023-01425-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00761-023-01425-7

Schlüsselwörter

Keywords

Search

Navigation