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

Leena Halim; Marco Romano; Reuben McGregor; Isabel Correa; Polychronis Pavlidis; Nathali Grageda; Sec-Julie Hoong; Muhammed Yuksel; Wayel Jassem; Rosalind F. Hannen; Mark Ong; Olivia Mckinney; Bu'Hussain Hayee; Sophia N. Karagiannis; Nicholas Powell; Robert I. Lechler; Estefania Nova-Lamperti; Giovanna Lombardi

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

Leena Halim, Marco Romano, Reuben McGregor, Isabel Correa, Polychronis Pavlidis, Nathali Grageda, Sec-Julie Hoong, Muhammed Yuksel, Wayel Jassem, Rosalind F. Hannen, Mark Ong, Olivia Mckinney, Bu'Hussain Hayee, Sophia N. Karagiannis, Nicholas Powell, Robert I. Lechler, Estefania Nova-Lamperti, Giovanna Lombardi

Dermatology

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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.

Original language	English
Pages (from-to)	757-770
Number of pages	14
Journal	Cell Reports
Volume	20
Issue number	3
Early online date	18 Jul 2017
DOIs	https://doi.org/10.1016/j.celrep.2017.06.079
Publication status	Published - 18 Jul 2017

Keywords

Adult
Autocrine Communication/immunology
Female
Humans
Interleukin-2/immunology
Male
Melanoma/immunology
T-Lymphocytes, Regulatory/immunology
Th2 Cells/immunology
Tumor Microenvironment/immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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An Atlas of Human_HALIM_Publishedonline18July2017_GOLD VoR (CC BY)Final published version, 5.24 MBLicence: CC BY

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Halim, L., Romano, M., McGregor, R., Correa, I., Pavlidis, P., Grageda, N., Hoong, S.-J., Yuksel, M., Jassem, W., Hannen, R. F., Ong, M., Mckinney, O., Hayee, BH., Karagiannis, S. N., Powell, N., Lechler, R. I., Nova-Lamperti, E., & Lombardi, G. (2017). An Atlas of Human Regulatory T Helper-like Cells Reveals Features of Th2-like Tregs that Support a Tumorigenic Environment. Cell Reports, 20(3), 757-770. https://doi.org/10.1016/j.celrep.2017.06.079

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title = "An Atlas of Human Regulatory T Helper-like Cells Reveals Features of Th2-like Tregs that Support a Tumorigenic Environment",

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 = "Adult, Autocrine Communication/immunology, Female, Humans, Interleukin-2/immunology, Male, Melanoma/immunology, T-Lymphocytes, Regulatory/immunology, Th2 Cells/immunology, Tumor Microenvironment/immunology",

author = "Leena Halim and Marco Romano and Reuben McGregor and Isabel Correa and Polychronis Pavlidis and Nathali Grageda and Sec-Julie Hoong and Muhammed Yuksel and Wayel Jassem and Hannen, {Rosalind F.} and Mark Ong and Olivia Mckinney and Bu'Hussain Hayee and Karagiannis, {Sophia N.} and Nicholas Powell and Lechler, {Robert I.} and Estefania Nova-Lamperti and Giovanna Lombardi",

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month = jul,

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doi = "10.1016/j.celrep.2017.06.079",

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Halim, L, Romano, M , McGregor, R, Correa, I, Pavlidis, P , Grageda, N, Hoong, S-J, Yuksel, M, Jassem, W, Hannen, RF, Ong, M, Mckinney, O, Hayee, BH , Karagiannis, SN , Powell, N , Lechler, RI , Nova-Lamperti, E & Lombardi, G 2017, 'An Atlas of Human Regulatory T Helper-like Cells Reveals Features of Th2-like Tregs that Support a Tumorigenic Environment', Cell Reports, vol. 20, no. 3, pp. 757-770. https://doi.org/10.1016/j.celrep.2017.06.079

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T1 - An Atlas of Human Regulatory T Helper-like Cells Reveals Features of Th2-like Tregs that Support a Tumorigenic Environment

AU - Halim, Leena

AU - Romano, Marco

AU - McGregor, Reuben

AU - Correa, Isabel

AU - Pavlidis, Polychronis

AU - Grageda, Nathali

AU - Hoong, Sec-Julie

AU - Yuksel, Muhammed

AU - Jassem, Wayel

AU - Hannen, Rosalind F.

AU - Ong, Mark

AU - Mckinney, Olivia

AU - Hayee, Bu'Hussain

AU - Karagiannis, Sophia N.

AU - Powell, Nicholas

AU - Lechler, Robert I.

AU - Nova-Lamperti, Estefania

AU - Lombardi, Giovanna

PY - 2017/7/18

Y1 - 2017/7/18

N2 - 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.

AB - 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.

KW - Adult

KW - Autocrine Communication/immunology

KW - Female

KW - Humans

KW - Interleukin-2/immunology

KW - Male

KW - Melanoma/immunology

KW - T-Lymphocytes, Regulatory/immunology

KW - Th2 Cells/immunology

KW - Tumor Microenvironment/immunology

U2 - 10.1016/j.celrep.2017.06.079

DO - 10.1016/j.celrep.2017.06.079

M3 - Article

C2 - 28723576

SN - 2211-1247

VL - 20

SP - 757

EP - 770

JO - Cell Reports

JF - Cell Reports

IS - 3

ER -

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

Abstract

Keywords

UN SDGs

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