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Cell Rep. 2017 Jul 18;20(3):757-770. doi: 10.1016/j.celrep.2017.06.079.

An Atlas of Human Regulatory T Helper-like Cells Reveals Features of Th2-like Tregs that Support a Tumorigenic Environment.

Author information

1
MRC Centre for Transplantation, King's College London, Guy's Hospital, SE1 9RT London, UK.
2
St. John's Institute of Dermatology, King's College London, Guy's Hospital, SE1 9RT London, UK.
3
Institute of Liver Studies and Transplantation, King's College London, King's College Hospital, SE5 9RS London, UK.
4
Centre for Cell Biology and Cutaneous Research, The Blizard Institute, Barts and the London School of Medicine and Dentistry, E1 2AT London, UK.
5
Histology/Histopathology Laboratory, King's College Hospital, SE5 9RS London, UK.
6
Department of Gastroenterology, King's College Hospital, SE5 9RS London, UK.
7
MRC Centre for Transplantation, King's College London, Guy's Hospital, SE1 9RT London, UK; King's Health Partners, SE1 9RT London, UK.
8
MRC Centre for Transplantation, King's College London, Guy's Hospital, SE1 9RT London, UK. Electronic address: enovalamperti@gmail.com.
9
MRC Centre for Transplantation, King's College London, Guy's Hospital, SE1 9RT London, UK. Electronic address: giovanna.lombardi@kcl.ac.uk.

Abstract

Regulatory T cells (Tregs) play a pivotal role in maintaining immunological tolerance, but they can also play a detrimental role by preventing antitumor responses. Here, we characterized T helper (Th)-like Treg subsets to further delineate their biological function and tissue distribution, focusing on their possible contribution to disease states. RNA sequencing and functional assays revealed that Th2-like Tregs displayed higher viability and autocrine interleukin-2 (IL-2)-mediated activation than other subsets. Th2-like Tregs were preferentially found in tissues rather than circulation and exhibited the highest migratory capacity toward chemokines enriched at tumor sites. These cellular responses led us to hypothesize that this subset could play a role in maintaining a tumorigenic environment. Concurrently, Th2-like Tregs were enriched specifically in malignant tissues from patients with melanoma and colorectal cancer compared to healthy tissue. Overall, our results suggest that Th2-like Tregs may contribute to a tumorigenic environment due to their increased cell survival, higher migratory capacity, and selective T-effector suppressive ability.

KEYWORDS:

T helper-like regulatory cells; chemokine receptor; immunoregulation; tumor immunity; tumor immunology

PMID:
28723576
PMCID:
PMC5529316
DOI:
10.1016/j.celrep.2017.06.079
[Indexed for MEDLINE]
Free PMC Article

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