Lee Jang-Jaer, Kao Kung-Chi, Chiu Yen-Ling, Jung Chiau-Jing, Liu Chung-Ji, Cheng Shih-Jung, Chang Yen-Liang, Ko Jenq-Yuh, Chia Jean-San
Department of Oral Maxillofacial Surgery, National Taiwan University Hospital, Taipei 100, Taiwan.
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
J Immunol. 2017 Jul 15;199(2):467-476. doi: 10.4049/jimmunol.1601815. Epub 2017 Jun 9.
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 and 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 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 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.
人类口腔鳞状细胞癌（OSCC）构成了一个富含趋化因子（如CCL20）的炎症微环境，这些趋化因子促进癌细胞侵袭和肿瘤进展。我们发现，在OSCC中，[此处原文缺失相关基因名称]与[此处原文缺失相关基因名称]mRNA的表达之间存在相关性。因此，我们推测OSCC可能有利于招募和保留表达CCL20受体CCR6的调节性T（Treg）细胞。有趣的是，大多数（约60%）外周血Treg细胞表达CCR6，且CCR6⁺ Treg细胞表现出活化的效应/记忆表型。相比之下，发现相当一部分（>30%）CCR6⁻ Treg细胞是CD45RA⁺初始Treg细胞。与CCR6⁻初始或记忆Treg细胞相比，CCR6⁺ Treg细胞表现出更强的抑制活性，并且显示出更高的FOXP3表达以及在[此处原文缺失相关基因名称]基因的Treg特异性去甲基化区域的更低甲基化水平。在临床分期早期或晚期的OSCC患者的引流淋巴结和肿瘤浸润淋巴细胞中也发现了CCR6⁺ Treg细胞的这种优势。此外，从肿瘤浸润淋巴细胞或引流淋巴结中分离出的CCR6⁺ Treg细胞在体外保持了与其从外周血中分离出的对应细胞相似的表型和抑制特性。这些结果表明，CCR6标记了人类中具有卓越抑制活性的活化效应或记忆Treg表型。
