Enrichment of human CCR6+ regulatory t cells with superior suppressive activity in oral cancer

Jang Jaer Lee, Kung Chi Kao, Yen Ling Chiu, Chiau Jing Jung, Chung Ji Liu, Shih Jung Cheng, Yen Liang Chang, Jenq Yuh Ko, Jean San Chia

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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 (?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.

Original languageEnglish
Pages (from-to)467-476
Number of pages10
JournalJournal of Immunology
Volume199
Issue number2
DOIs
Publication statusPublished - Jul 15 2017

    Fingerprint

ASJC Scopus subject areas

  • Immunology

Cite this

Lee, J. J., Kao, K. C., Chiu, Y. L., Jung, C. J., Liu, C. J., Cheng, S. J., Chang, Y. L., Ko, J. Y., & Chia, J. S. (2017). Enrichment of human CCR6+ regulatory t cells with superior suppressive activity in oral cancer. Journal of Immunology, 199(2), 467-476. https://doi.org/10.4049/jimmunol.1601815