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High-Dimensional Mass Cytometric Analysis Reveals an Increase in Effector Regulatory T Cells as a Distinguishing Feature of Colorectal Tumors

Samuel E. Norton, Kirsten A. Ward-Hartstonge, John L. McCall, Julia K. H. Leman, Edward S. Taylor, Fran Munro, Michael A. Black, Barbara Fazekas de St. Groth, Helen M. McGuire and Roslyn A. Kemp
J Immunol February 6, 2019, ji1801368; DOI: https://doi.org/10.4049/jimmunol.1801368
Samuel E. Norton
Department of Microbiology and Immunology, Otago School of Biomedical Sciences, The University of Otago, Dunedin 9010, New Zealand;
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Kirsten A. Ward-Hartstonge
Department of Microbiology and Immunology, Otago School of Biomedical Sciences, The University of Otago, Dunedin 9010, New Zealand;
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John L. McCall
Department of Surgical Sciences, Dunedin School of Medicine, The University of Otago, Dunedin 9010, New Zealand;
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Julia K. H. Leman
Department of Microbiology and Immunology, Otago School of Biomedical Sciences, The University of Otago, Dunedin 9010, New Zealand;
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Edward S. Taylor
Department of Microbiology and Immunology, Otago School of Biomedical Sciences, The University of Otago, Dunedin 9010, New Zealand;
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Fran Munro
Department of Surgical Sciences, Dunedin School of Medicine, The University of Otago, Dunedin 9010, New Zealand;
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Michael A. Black
Department of Biochemistry, Dunedin School of Medical Sciences, University of Otago, Dunedin 9010, New Zealand;
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Barbara Fazekas de St. Groth
Ramaciotti Facility for Human Systems Biology, The University of Sydney and Centenary Institute, Sydney, New South Wales 2006, Australia; ¶Discipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales 2006, Australia; and ‖Charles Perkins Centre, University of Sydney, Sydney, New South Wales 2006, Australia
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Helen M. McGuire
Ramaciotti Facility for Human Systems Biology, The University of Sydney and Centenary Institute, Sydney, New South Wales 2006, Australia; ¶Discipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales 2006, Australia; and ‖Charles Perkins Centre, University of Sydney, Sydney, New South Wales 2006, Australia
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Roslyn A. Kemp
Department of Microbiology and Immunology, Otago School of Biomedical Sciences, The University of Otago, Dunedin 9010, New Zealand;
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Abstract

T cell infiltration of tumors plays an important role in determining colorectal cancer disease progression and has been incorporated into the Immunoscore prognostic tool. In this study, mass cytometry was used to demonstrate a significant increase in the frequency of both conventional CD25+FOXP3+CD127lo regulatory T cells (Tregs) as well as BLIMP-1+ Tregs in the tumor compared with nontumor bowel (NTB) of the same patients. Network cluster analyses using SCAFFoLD, VorteX, and CITRUS revealed that an increase in BLIMP-1+ Tregs was a single distinguishing feature of the tumor tissue compared with NTB. BLIMP-1+ Tregs represented the most significantly enriched T cell population in the tumor compared with NTB. The enrichment of ICOS, CD45RO, PD-1, PDL-1, LAG-3, CTLA-4, and TIM-3 on BLIMP-1+ Tregs suggests that BLIMP-1+ Tregs have a more activated phenotype than conventional Tregs and may play a role in antitumor immune responses.

Footnotes

  • The work was supported by the Cancer Research Trust, Lotteries Health Research New Zealand, and the University of Otago School of Biomedical Sciences. K.A.W.-H. was supported by a Lotteries Health Research Ph.D. Scholarship. E.S.T. and J.K.H.L. were supported by University of Otago Ph.D. and master’s scholarships, respectively. H.M.M. was supported by an Australian National Health and Medical Research Council Early Career Fellowship (GNT1037298). R.A.K. was supported by the New Zealand Society for Oncology-Roche Translational Research Fellowship.

  • The online version of this article contains supplemental material.

  • Received October 10, 2018.
  • Accepted January 14, 2019.
  • Copyright © 2019 by The American Association of Immunologists, Inc.

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The Journal of Immunology: 202 (5)
The Journal of Immunology
Vol. 202, Issue 5
1 Mar 2019
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High-Dimensional Mass Cytometric Analysis Reveals an Increase in Effector Regulatory T Cells as a Distinguishing Feature of Colorectal Tumors
Samuel E. Norton, Kirsten A. Ward-Hartstonge, John L. McCall, Julia K. H. Leman, Edward S. Taylor, Fran Munro, Michael A. Black, Barbara Fazekas de St. Groth, Helen M. McGuire, Roslyn A. Kemp
The Journal of Immunology February 6, 2019, ji1801368; DOI: 10.4049/jimmunol.1801368

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High-Dimensional Mass Cytometric Analysis Reveals an Increase in Effector Regulatory T Cells as a Distinguishing Feature of Colorectal Tumors
Samuel E. Norton, Kirsten A. Ward-Hartstonge, John L. McCall, Julia K. H. Leman, Edward S. Taylor, Fran Munro, Michael A. Black, Barbara Fazekas de St. Groth, Helen M. McGuire, Roslyn A. Kemp
The Journal of Immunology February 6, 2019, ji1801368; DOI: 10.4049/jimmunol.1801368
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Print ISSN 0022-1767        Online ISSN 1550-6606