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

• DOI: 10.1016/j.celrep.2017.06.079
• Publication Date: 2017-07-18T22:47:21Z
• Authors: 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. Karagia...; Nicholas Powell; Robert I. Lechler; Estefania Nova-La...; Giovanna Lombardi
• Keywords: EXPRESSION; Resource; Adult; Male; Melanoma/immunology; immunoregulation; QH301-705.5; T-Lymphocytes; 610; T-Lymphocytes, Regulatory/immunology; IMMUNITY; Th2 Cells/immunology; 0601 Biochemistry and Cell Biology; T helper-like regulatory cells; T-Lymphocytes, Regulatory; COLORECTAL-CANCER; 03 medical and health sciences; Th2 Cells; 0302 clinical medicine; 616; Autocrine Communication/immunology; Tumor Microenvironment; Tumor Microenvironment/immunology; Humans; tumor immunology; Biology (General); Melanoma; Science & Technology; TRANSCRIPTION FACTOR FOXP3; MEMORY; chemokine receptor; Cell Biology; Regulatory; tumor immunity; 3. Good health; Interleukin-2/immunology; Autocrine Communication; SURVIVAL; Interleukin-2; Regulatory/immunology; TH2 CELLS; Female; Life Sciences & Biomedicine; TUMOR MICROENVIRONMENT; GASTRIC-CANCER; RESPONSES

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.