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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