Review
. 2020 Oct; 9(10):e1183.
doi: 10.1002/cti2.1183.

Immune contexture analysis in immuno-oncology: applications and challenges of multiplex fluorescent immunohistochemistry

Reshma Shakya 1 Tam Hong Nguyen 2 Nigel Waterhouse 2 Rajiv Khanna 1 
Affiliations
  • PMID: 33072322
  •     159 References
  •     4 citations

Abstract

The tumor microenvironment is an integral player in cancer initiation, tumor progression, response and resistance to anti-cancer therapy. Understanding the complex interactions of tumor immune architecture (referred to as 'immune contexture') has therefore become increasingly desirable to guide our approach to patient selection, clinical trial design, combination therapies, and patient management. Quantitative image analysis based on multiplexed fluorescence immunohistochemistry and deep learning technologies are rapidly developing to enable researchers to interrogate complex information from the tumor microenvironment and find predictive insights into treatment response. Herein, we discuss current developments in multiplexed fluorescence immunohistochemistry for immune contexture analysis, and their application in immuno-oncology, and discuss challenges to effectively use this technology in clinical settings. We also present a multiplexed image analysis workflow to analyse fluorescence multiplexed stained tumor sections using the Vectra Automated Digital Pathology System together with FCS express flow cytometry software. The benefit of this strategy is that the spectral unmixing accurately generates and analyses complex arrays of multiple biomarkers, which can be helpful for diagnosis, risk stratification, and guiding clinical management of oncology patients.

Keywords: FCS express image cytometry; immune profiling; multiplexed fluorescent immunohistochemistry; quantitative digital pathology; tumor microenvironment; vectra.

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Commentary: Roles for Pathologists in a High-throughput Image Analysis Team.
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Erratum to: Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance.
Vasiliki Pelekanou, Daniel E Carvajal-Hausdorf, +7 authors, David L Rimm.
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Mel Greaves, Carlo C Maley.
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Spatial Mapping of Myeloid Cells and Macrophages by Multiplexed Tissue Staining.
Joshua Saylor, Zhaoxuan Ma, +9 authors, Beatrice S Knudsen.
Front Immunol, 2019 Jan 09; 9. PMID: 30619287    Free PMC article.
Multiplexed Immunohistochemistry and Digital Pathology as the Foundation for Next-Generation Pathology in Melanoma: Methodological Comparison and Future Clinical Applications.
Yannick Van Herck, Asier Antoranz, +4 authors, Francesca Maria Bosisio.
Front Oncol, 2021 Apr 16; 11. PMID: 33854972    Free PMC article.
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Next-Generation Digital Histopathology of the Tumor Microenvironment.
Felicitas Mungenast, Achala Fernando, +4 authors, Rupert C Ecker.
Genes (Basel), 2021 May 01; 12(4). PMID: 33917241    Free PMC article.
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Challenges and Opportunities in the Statistical Analysis of Multiplex Immunofluorescence Data.
Christopher M Wilson, Oscar E Ospina, +6 authors, Brooke L Fridley.
Cancers (Basel), 2021 Jul 03; 13(12). PMID: 34204319    Free PMC article.
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Comparison of liver biopsies before and after direct-acting antiviral therapy for hepatitis C and correlation with clinical outcome.
Omar A Saldarriaga, Bradley Dye, +6 authors, Heather L Stevenson.
Sci Rep, 2021 Jul 17; 11(1). PMID: 34267267    Free PMC article.