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Multispectral imaging for quantitative and compartment-specific immune infiltrates reveals distinct immune profiles that classify lung cancer patients.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
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2018 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 244, no 4, p. 421-431Article in journal (Refereed) Published
Abstract [en]

Semiquantitative assessment of immune markers by immunohistochemistry (IHC) has significant limitations for describing the diversity of the immune response in cancer. Therefore, we evaluated a fluorescence-based multiplexed immunohistochemical method in combination with a multispectral imaging system to quantify immune infiltrates in situ in the environment of non-small-cell lung cancer (NSCLC). A tissue microarray including 57 NSCLC cases was stained with antibodies against CD8, CD20, CD4, FOXP3, CD45RO, and pan-cytokeratin, and immune cells were quantified in epithelial and stromal compartments. The results were compared with those of conventional IHC, and related to corresponding RNA-sequencing (RNAseq) expression values. We found a strong correlation between the visual and digital quantification of lymphocytes for CD45RO (correlation coefficient: r = 0.52), FOXP3 (r = 0.87), CD4 (r = 0.79), CD20 (r = 0.81) and CD8 (r = 0.90) cells. The correlation with RNAseq data for digital quantification (0.35-0.65) was comparable to or better than that for visual quantification (0.38-0.58). Combination of the signals of the five immune markers enabled further subpopulations of lymphocytes to be identified and localized. The specific pattern of immune cell infiltration based either on the spatial distribution (distance between regulatory CD8(+) T and cancer cells) or the relationships of lymphocyte subclasses with each other (e.g. cytotoxic/regulatory cell ratio) were associated with patient prognosis. In conclusion, the fluorescence multiplexed immunohistochemical method, based on only one tissue section, provided reliable quantification and localization of immune cells in cancer tissue. The application of this technique to clinical biopsies can provide a basic characterization of immune infiltrates to guide clinical decisions in the era of immunotherapy.

Place, publisher, year, edition, pages
2018. Vol. 244, no 4, p. 421-431
Keywords [en]
PD-L1, checkpoint therapy, deep-learning microscopy, digital pathology, prognosis, tumour microenvironment
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:uu:diva-343644DOI: 10.1002/path.5026ISI: 000428213800006PubMedID: 29282718OAI: oai:DiVA.org:uu-343644DiVA, id: diva2:1186473
Funder
Swedish Cancer SocietyAvailable from: 2018-02-28 Created: 2018-02-28 Last updated: 2018-06-20Bibliographically approved

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Mezheyeuski, ArturBackman, MaxDjureinovic, DijanaSjöblom, TobiasMicke, Patrick

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