CCL20 (the ligand for CCR6) is expressed in oral squamous cell carcinoma and correlates with FOXP3 expression. Lee et al. examined the phenotypic properties of CCR6+ and CCR6- Treg cells. CCR6+ T cells recruited to the tumor had an effector/memory phenotype that exhibited a stronger immune suppressive effect compared to CCR6- memory or naive Tregs.
Human 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 ( approximately 60%) peripheral blood Treg cells express CCR6, and CCR6+ Treg cells exhibit an activated effector/memory phenotype. In contrast, a significant portion (>30%) of CCR6- Treg cells were found to be CD45RA+ naive Treg cells. Compared to CCR6- 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 tumor-infiltrating 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.
Author Info: (1) Department of Oral Maxillofacial Surgery, National Taiwan University Hospital, Taipei 100, Taiwan. (2) Graduate Institute of Immunology, College of Medicine, National Taiwan Un
Author Info: (1) Department of Oral Maxillofacial Surgery, National Taiwan University Hospital, Taipei 100, Taiwan. (2) Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei 100, Taiwan. (3) Department of Nephrology, Far Eastern Memorial Hospital, Taipei 220, Taiwan. Graduate Program of Biomedical Informatics, Yuan Ze University, Taoyuan 320, Taiwan. (4) Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. (5) Department of Oral Maxillofacial Surgery, Taipei MacKay Memorial Hospital, Taipei 104, Taiwan. (6) Department of Oral Maxillofacial Surgery, National Taiwan University Hospital, Taipei 100, Taiwan. (7) Department of Otolaryngology, Fu Jen Catholic University College of Medicine, New Taipei City 24205, Taiwan; and. (8) Department of Otolaryngology, National Taiwan University Hospital, Taipei 100, Taiwan. (9) Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei 100, Taiwan; chiajs@ntu.edu.tw.
