JANG-JAER LEEKao K.-C.Chiu Y.-L.Jung C.-J.Liu C.-J.SHIH-JUNG CHENGChang Y.-L.JENG-YUH KOJEAN-SAN CHIA2021-07-072021-07-0720170022-1767https://www.scopus.com/inward/record.uri?eid=2-s2.0-85023207944&doi=10.4049%2fjimmunol.1601815&partnerID=40&md5=6cd434a122540c40ac0d1704d057d296https://scholars.lib.ntu.edu.tw/handle/123456789/570115Human oral squamous cell carcinoma (OSCC) constitutes an inflammatory microenvironment enriched with chemokines such as CCL20, which promote cancer cell invasion and tumor progression. We found that in OSCC there is a correlation between the expression of CCL20 and FOXP3 mRNA. Therefore, we hypothesized that OSCC may favor the recruitment and retention of regulatory T (Treg) cells that express the CCL20 receptor, CCR6. Interestingly, most (?60%) peripheral blood Treg cells express CCR6, and CCR6+ Treg cells exhibit an activated effector/memory phenotype. In contrast, a significant portion (>30%) of CCR62 Treg cells were found to be CD45RA+ naive Treg cells. Compared to CCR62 naive or memory Treg cells, CCR6+ Treg cells exhibit stronger suppressive activity and display higher FOXP3 expression along with lower methylation at the Treg-specific demethylated region of the FOXP3 gene. This predominance of CCR6+ Treg cells was also found in the draining lymph nodes and tumorinfiltrating lymphocytes of OSCC patients with early or late clinical staging. Moreover, CCR6+ Treg cells isolated from tumor-infiltrating lymphocytes or draining lymph nodes maintained similar phenotypic and suppressive characteristics ex vivo as did their counterparts isolated from peripheral blood. These results suggest that CCR6 marks activated effector or memory Treg phenotypes with superior suppressive activity in humans. ? 2017 by The American Association of Immunologists, Inc.[SDGs]SDG3chemokine receptor CCR6; macrophage inflammatory protein 3alpha; messenger RNA; transcription factor FOXP3; CCL20 protein, human; CD45 antigen; chemokine receptor CCR6; forkhead transcription factor; FOXP3 protein, human; macrophage inflammatory protein 3alpha; Article; cancer growth; cancer staging; CCL20 gene; controlled study; DNA methylation; FOXP3 gene; gene; gene expression; genetic association; human; human cell; human tissue; mouth cancer; priority journal; regulatory T lymphocyte; T lymphocyte activation; tumor associated leukocyte; tumor microenvironment; adult; cytology; deficiency; female; genetics; immunological memory; immunology; lymph node; male; methylation; middle aged; mouth tumor; pathology; physiology; regulatory T lymphocyte; squamous cell carcinoma; Adult; Antigens, CD45; Carcinoma, Squamous Cell; Chemokine CCL20; Female; Forkhead Transcription Factors; Humans; Immunologic Memory; Lymph Nodes; Lymphocytes, Tumor-Infiltrating; Male; Methylation; Middle Aged; Mouth Neoplasms; Receptors, CCR6; T-Lymphocytes, Regulatoryjournal article10.4049/jimmunol.1601815286002872-s2.0-85023207944