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Oncotarget. 2019 Jun 04;10(38):3592-3604. doi: 10.18632/oncotarget.26911. eCollection 2019 Jun 04.

Flow based single cell analysis of the immune landscape distinguishes Barrett's esophagus from adjacent normal tissue.

Oncotarget

Moen Sen, Friedrich Hahn, Taylor A Black, Maureen DeMarshall, Warren Porter, Eileen Snowden, Stephanie S Yee, Frances Tong, Mitchell Ferguson, Emylee N Fleshman, Hiroshi Nakagawa, Gary W Falk, Gregory G Ginsberg, Michael L Kochman, Rainer Blaesius, Anil K Rustgi, Erica L Carpenter

Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  2. Department of Genomic Sciences, BD Technologies and Innovation, Research Triangle Park, Durham, North Carolina, USA.
  3. Division of Gastroenterology, Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

PMID: 31217895 PMCID: PMC6557213 DOI: 10.18632/oncotarget.26911

Abstract

Barrett's esophagus (BE) is metaplasia of the squamous epithelium to a specialized columnar epithelium. BE progresses through low- and high-grade dysplasia before developing into esophageal adenocarcinoma. The BE microenvironment is not well defined. We compare 12 human clinical BE and adjacent normal squamous epithelium biopsies using single cell immunophenotyping by flow cytometry. A cassette of 19 epithelial and immune cell markers was used to detect differences between cellular compartments in normal and BE tissues. We found that the BE microenvironment has an immunological landscape distinct from adjacent normal epithelium. BE has an increased percentage of epithelial cells with a concomitant decrease in the percentage of immune cells, accompanied by a shift in the immune landscape from a predominantly T cell rich microenvironment in normal tissue to a B cell rich landscape in BE tissue. Hierarchical clustering separates BE and normal samples into two discrete groups based upon our 19-marker panel, but also reveals unexpected, shared phenotypes for three patients. Our results suggest that flow based single cell analysis may have the potential for revealing clinically relevant differences between BE and normal adjacent tissue, and that surface immunophenotypes could identify specific subpopulations from dysplastic tissue for further investigation.

Keywords: Barrett’s esophagus; flow cytometry; immune cells; microenvironment; single cell

Conflict of interest statement

CONFLICTS OF INTEREST E.L.C. receives research support from BD Technologies and Innovations, Janssen, and Merck and travel expenses from AstraZeneca and Foundation Medicine. G.W.F. receives research f

References

  1. Br J Cancer. 2001 Aug 17;85(4):473-83 - PubMed
  2. Gut. 2002 Apr;50(4):451-9 - PubMed
  3. J Pathol. 2005 Nov;207(3):269-76 - PubMed
  4. Differentiation. 1991 Apr;46(3):209-21 - PubMed
  5. Am J Epidemiol. 2008 Aug 1;168(3):237-49 - PubMed
  6. J Cell Mol Med. 2009 Sep;13(9B):3826-33 - PubMed
  7. Clin Gastroenterol Hepatol. 2010 Mar;8(3):235-44; quiz e32 - PubMed
  8. Gut. 2012 Jul;61(7):970-6 - PubMed
  9. Cancer Cell. 2012 Jan 17;21(1):36-51 - PubMed
  10. Histopathology. 2012 Nov;61(5):769-76 - PubMed
  11. PLoS One. 2014 Aug 29;9(8):e105602 - PubMed
  12. Cancer Immunol Res. 2015 Oct;3(10):1123-1129 - PubMed
  13. Appl Immunohistochem Mol Morphol. 2016 Oct;24(9):633-638 - PubMed
  14. Nat Genet. 2015 Sep;47(9):1038-1046 - PubMed
  15. Nat Genet. 2015 Sep;47(9):1047-55 - PubMed
  16. Clin Cancer Res. 2015 Nov 15;21(22):5047-56 - PubMed
  17. Scand J Clin Lab Invest Suppl. 2016;245:S63-9 - PubMed
  18. PLoS One. 2016 Aug 25;11(8):e0161781 - PubMed
  19. Wiley Interdiscip Rev Syst Biol Med. 2017 Mar;9(2): - PubMed
  20. Mol Cancer Res. 2017 Apr;15(4):429-438 - PubMed
  21. Am J Cancer Res. 2017 May 01;7(5):1016-1036 - PubMed
  22. Nat Rev Cancer. 2017 Oct;17(10):594-604 - PubMed
  23. Iran J Pathol. 2017 Fall;12(4):339-347 - PubMed
  24. Gastroenterology. 2018 Jul;155(1):156-167 - PubMed
  25. Trends Cell Biol. 2018 Sep;28(9):738-748 - PubMed
  26. Cancer Res. 1984 Jun;44(6):2628-33 - PubMed
  27. Immunol Rev. 1995 Jun;145:229-50 - PubMed
  28. Dev Biol. 1999 Feb 1;206(1):88-99 - PubMed

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